Hepcidin defense patterns in intestine of mandarin fish (Siniperca chuatsi) against Aeromonas hydrophila infection.

Bacterial septicemia caused by Aeromonas hydrophila is one of the common bacterial diseases in aquaculture. Antimicrobial peptides, including hepcidin, are key components of the innate immune system in fish, playing a role in defense against pathogens. This study investigated the defense patterns of hepcidin in mandarin fish (Siniperca chuatsi) following A. hydrophila infection using gene expression analysis and in vitro antibacterial assays. We measured changes in the expression of iron metabolism-related genes (hepcidin, fpn, ftn, tf, tfr1) and immune-related genes (il-1ß, il-6, il-8, il-10, tnf-α, socs3, nkap, tlr1, tlr2) in the intestine post-infection. MBC experiment demonstrated that the hepcidin synthetic peptide has an inhibitory effect on the growth of V. parahaemolyticus (32 µg/ml), A. hydrophilus (64 µg/ml), and F. columnaris (128 µg/ml), but not E. tarda (>256 µg/ml). After A. hydrophilus challenge, fpn, tf and tfr1 with peak expression at 24 hpi (2.75), 12 hpi (4.43) and 6 hpi (7.41), respectively. Hepcidin and ftn expression was highest at 48 hpi (115.01) and 72 hpi (4.16). The Fe2+ content peaked at 6 hpi (2.64 µmol/l) and reached its lowest at 12 hpi (1.12 µmol/l) in the intestine. After pathogen challenge, il-1ß, il-8, socs3, tlr2, and hepcidin showed trends of increased and then decreased, with peak expression at 72 hpi (5.13, 37.05, 3.08) and 48 hpi (5.35, 115.01), respectively. These findings suggested that hepcidin plays a key role in the defense against A. hydrophila: initially restricting bacterial growth through iron metabolism (0-48 hpi), and later modulating immune responses via the TNF (by inducing il-1ß and socs3) and Toll-like receptor pathways (by inducing il-8 and tlr2) (48-96 hpi). This study provides novel insights into the immune function of hepcidin in fish and its potential application in managing bacterial infections in aquaculture.

Characteristics of altered biventricular hemodynamics after arterial switch operation for patients with d-transposition of the great arteries with preserved ejection fraction: a four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) study.

Background: The long-term monitoring of biventricular function is essential to identify potential functional decline in patients following the arterial switch operation (ASO). The underlying pathophysiological mechanisms responsible for altered biventricular hemodynamics in ASO patients are not yet well understood. This study sought to: (I) compare the biventricular kinetic energy (KE) and vorticity of ASO patients and age- and sex-matched controls; (II) investigate the associations of four-dimensional (4D) flow biventricular hemodynamics parameters and neo-aortic root dilation, supravalvular pulmonary stenosis, and pulmonary artery transvalvular pressure difference. Methods: A total of 34 patients with dextro-transposition of the great arteries (D-TGA) who underwent ASO, and 17 age- and gender-matched healthy controls were prospectively recruited for this study. All the subjects underwent cine and 4D flow and late gadolinium enhancement scans, and all the patients underwent echocardiography within two weeks of cardiovascular magnetic resonance (CMR) imaging. The following four flow components were analyzed: direct flow, retained inflow, delayed ejection flow, and residual volume. In addition, the following six phasic blood flow KE parameters, normalized to the end-diastolic volume (EDV) and vorticity, were analyzed for both the left ventricle (LV) and right ventricle (RV): peak systolic phase, average systolic phase, peak diastolic phase, average diastolic phase, peak E-wave phase, and peak A-wave phase. The independent sample Student's t-test, Mann-Whitney U-test, univariable and multivariable stepwise regression analyses, intra and inter-observer variability analyses were used to compare patients and controls. Results: In relation to the LV, the D-TGA patients had significantly decreased average vorticity, peak systolic vorticity, systolic vorticity, diastolic vorticity, and peak A-wave vorticity compared to the controls (all P<0.01). In relation to the RV, the pulmonary stenosis group had significantly increased peak E- and A-wave kinetic energy normalized to the end-diastolic volume (KEiEDV), and peak and average vorticity compared to the non-pulmonary stenosis group (all P<0.05). in the multivariable logistic regression model analysis, diastolic KEiEDV, peak E-wave KEiEDV peak A-wave KEiEDV, and average vorticity were associated a with transvalvular pressure difference (ß=13.54, P<0.001 for diastolic KEiEDV; ß=105.26, P<0.001 for peak E-wave KEiEDV; ß=-49.36, P=0.027 for peak A-wave KEiEDV; and ß=-56.37, P<0.001 for average vorticity). Conclusions: We found that 4D flow biventricular hemodynamics were more sensitive markers than the ejection fraction in the postoperative D-TGA patients. The RV diastolic KEiEDV parameters and average vorticity were risk factors for pulmonary artery obstruction in the multivariable model.

Effects of carbon and nitrogen availability on soil microbial respiration and its metabolic response in subtropical plantations.

We examined the metabolic response of microbial respiration to glucose addition with the topsoil (0-10 cm) from five plantation types, including Quercus glauca, Castanopsis kawakamii, Pinus massoniana, Phoebe bournei, and Cinnamomum camphora plantations, in the Sanming Forest Ecosystem National Field Observation and Research Station in Fujian Province. The results showed that glucose addition significantly increased microbial respiration by 82.4%-349.5%, with significant difference among tree species. In the control, microbial respiration significantly correlated with microbial biomass carbon, soil organic carbon, and the fungi/bacteria ratio, indicating that microbial metabolism was regulated by soil organic carbon content and was associated with microbial biomass and community structure in the absence of labile carbon supply. In the glucose addition treatment, microbial respiration positively correlated with soil total nitrogen, dissolved organic nitrogen, and mineral nitrogen, indicating that microbial metabolism was mainly constrained by soil nitrogen content and its availability in the presence of adequate labile carbon supply. The metabolic response of microbial respiration, as indicated by the ratio of microbial respiration in the glucose addition treatment to that in the control, was primarily affected by soil carbon/nitrogen ratio, with a decrease in the ratio leading to an increase in the microbial metabolic response. Additionally, soil pH played an important role in mediating microbial metabolic response. The effect of the content and availability of soil carbon and nitrogen on microbial respiration depended on whether microbes were carbon-limited. Soil carbon content media-ted microbial respiration when microbes were carbon-limited, whereas soil nitrogen content and availability mediated microbial respiration after the alleviation of microbial carbon limitation.

Inorganic nitrogen inhibits symbiotic nitrogen fixation through blocking NRAMP2-mediated iron delivery in soybean nodules.

Symbiotic nitrogen fixation (SNF) in legume-rhizobia serves as a sustainable source of nitrogen (N) in agriculture. However, the addition of inorganic N fertilizers significantly inhibits SNF, and the underlying mechanisms remain not-well understood. Here, we report that inorganic N disrupts iron (Fe) homeostasis in soybean nodules, leading to a decrease in SNF efficiency. This disruption is attributed to the inhibition of the Fe transporter genes Natural Resistance-Associated Macrophage Protein 2a and 2b (GmNRAMP2a&2b) by inorganic N. GmNRAMP2a&2b are predominantly localized at the tonoplast of uninfected nodule tissues, affecting Fe transfer to infected cells and consequently, modulating SNF efficiency. In addition, we identified a pair of N-signal regulators, nitrogen-regulated GARP-type transcription factors 1a and 1b (GmNIGT1a&1b), that negatively regulate the expression of GmNRAMP2a&2b, which establishes a link between N signaling and Fe homeostasis in nodules. Our findings reveal a plausible mechanism by which soybean adjusts SNF efficiency through Fe allocation in response to fluctuating inorganic N conditions, offering valuable insights for optimizing N and Fe management in legume-based agricultural systems.

Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro.

AIMS: Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), primarily constituted of α-synuclein (α-Syn). Microglial cells exhibit specific reactivity toward misfolded proteins such as α-Syn. However, the exact clearance mechanism and related molecular targets remain elusive. METHODS: BV2 cells, primary microglia from wild-type and MT1 knockout mice, and primary cortical neurons were utilized as experimental models. The study investigated relevant mechanisms by modulating microglial MT1 expression through small RNA interference (RNAi) and lentiviral overexpression techniques. Furthermore, pathological aggregation of α-Syn was induced using pre-formed fibrils (PFF) α-Syn. Co-immunoprecipitation, immunofluorescence, Western blot (WB), and quantitative real-time PCR were used to elucidate the mechanisms of molecular regulation. RESULTS: In this study, we elucidated the regulatory role of the melatonin receptor 1 (MT1) in the microglial phagocytic process. Following MT1 knockout, the ability of microglial cells to engulf latex beads and zymosan particles decreased, subsequently affecting the phagocytic degradation of fibrillar α-Syn by microglial cells. Furthermore, the loss of MT1 receptors in microglial cells exacerbates the aggregation of α-Syn in neurons induced by pre-formed fibrils (PFF) α-Syn. Mechanistically, MT1 influences the phagocytic function of microglial cells by regulating the Rubicon-dependent LC3-associated phagocytosis (LAP) pathway. CONCLUSION: Taken together, the results suggest the neuroprotective function of microglial cells in clearing α-Syn through MT1-mediated LAP, highlighting the potential key role of MT1 in pathogenic mechanisms associated with α-Syn.

Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment.

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

Recent Advances in the Glycolytic Processes Linked to Tumor Metastasis.

The main cause of cancer-related fatalities is cancer metastasis to other body parts, and increased glycolysis is crucial for cancer cells to maintain their elevated levels of growth and energy requirements, ultimately facilitating the invasion and spread of tumors. The Warburg effect plays a significant role in the advancement of cancer, and focusing on the suppression of aerobic glycolysis could offer a promising strategy for anti-cancer treatment. Various glycolysis processes are associated with tumor metastasis, primarily involving non-coding RNA (ncRNAs), signaling pathways, transcription factors, and more. Various categories of noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have shown promise in influencing glucose metabolism associated with the spread of tumors. Additionally, circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) predominantly act as competitive endogenous RNAs (ceRNAs) by sequestering microRNAs, thereby modulating the expression of target genes and exerting significant influence on the metabolic processes of cancerous cells. Furthermore, the process of tumor metastasis through glycolysis also encompasses various signaling pathways (such as PI3K/AKT, HIF, Wnt/ß- Catenin, and ERK, among others) and transcription factors. This article delineates the primary mechanisms through which non-coding RNAs, signaling pathways, and transcription factors contribute to glycolysis in tumor metastasis. It also investigates the potential use of these factors as prognostic markers and targets for cancer treatment. The manuscript also explores the innovative applications of specific traditional Chinese medicine and clinical Western medications in inhibiting tumor spread through glycolysis mechanisms, offering potential as new candidates for anti-cancer drugs.

Correlation between circulating lipoprotein(a) levels and cardiovascular events risk in patients with type 2 diabetes.

Background: High circulatory lipoprotein(a) [Lp(a)] concentration promotes atherosclerosis; however, its efficacy in predicting the extent of atherosclerotic coronary heart disease (CHD) with coronary artery obstruction and major adverse cardiovascular events (MACEs) in diabetic patients remains questionable. This study aimed to examine whether elevated circulating Lp(a) levels exacerbate CHD and to assess their utility in predicting MACEs in individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods: In total, 4332 patients diagnosed with T2DM who underwent coronary angiography (CAG) were included and categorized into two groups (CHD and non-CHD) based on the CAG results. We used a correlation analysis to explore the potential links between the levels of circulating Lp(a) and CHD severity. Cox regression analysis was performed to evaluate MACEs. Results: The concentrations of circulating Lp(a) were markedly elevated in the CHD group and positively correlated with disease severity. Our results indicate that elevated circulating Lp(a) is a crucial risk factor that significantly contributes to both the progression and severity of CHD. The differences between the two groups are evident in the risk of CHD occurrence [odds ratio (OR) = 1.597, 95 % confidence interval (CI): 1.354-1.893, p < 0.001], the different levels of vessel involvement (OR = 1.908 for triple-vessel vs. single-vessel disease, 95 % CI: 1.401-2.711, p < 0.001), and their relation to the Gensini Score (OR = 2.002 for high vs. low GS, 95 % CI: 1.514-2.881, p < 0.001). Over the course of the 7-year follow-up period, the multivariate Cox regression analysis indicated that increased levels Lp(a) levels are independently associated with the occurrence of MACEs [hazard ratio (HR) = 1.915, 95 % CI: 1.571-2.493, p < 0.001]. Conclusion: We confirmed a positive correlation among circulating Lp(a) levels, CHD lesions count, and Gensini scores. Moreover, Lp(a) levels have predictive significance for the occurrence of MACEs in T2DM patients.

Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology.

OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

Highly sensitive detection platform-based diagnosis of oesophageal squamous cell carcinoma in China: a multicentre, case-control, diagnostic study.

BACKGROUND: Early detection and screening of oesophageal squamous cell carcinoma rely on upper gastrointestinal endoscopy, which is not feasible for population-wide implementation. Tumour marker-based blood tests offer a potential alternative. However, the sensitivity of current clinical protein detection technologies is inadequate for identifying low-abundance circulating tumour biomarkers, leading to poor discrimination between individuals with and without cancer. We aimed to develop a highly sensitive blood test tool to improve detection of oesophageal squamous cell carcinoma. METHODS: We designed a detection platform named SENSORS and validated its effectiveness by comparing its performance in detecting the selected serological biomarkers MMP13 and SCC against ELISA and electrochemiluminescence immunoassay (ECLIA). We then developed a SENSORS-based oesophageal squamous cell carcinoma adjunct diagnostic system (with potential applications in screening and triage under clinical supervision) to classify individuals with oesophageal squamous cell carcinoma and healthy controls in a retrospective study including participants (cohort I) from Sun Yat-sen University Cancer Center (SYSUCC; Guangzhou, China), Henan Cancer Hospital (HNCH; Zhengzhou, China), and Cancer Hospital of Shantou University Medical College (CHSUMC; Shantou, China). The inclusion criteria were age 18 years or older, pathologically confirmed primary oesophageal squamous cell carcinoma, and no cancer treatments before serum sample collection. Participants without oesophageal-related diseases were recruited from the health examination department as the control group. The SENSORS-based diagnostic system is based on a multivariable logistic regression model that uses the detection values of SENSORS as the input and outputs a risk score for the predicted likelihood of oesophageal squamous cell carcinoma. We further evaluated the clinical utility of the system in an independent prospective multicentre study with different participants selected from the same three institutions. Patients with newly diagnosed oesophageal-related diseases without previous cancer treatment were enrolled. The inclusion criteria for healthy controls were no obvious abnormalities in routine blood and tumour marker tests, no oesophageal-associated diseases, and no history of cancer. Finally, we assessed whether classification could be improved by integrating machine-learning algorithms with the system, which combined baseline clinical characteristics, epidemiological risk factors, and serological tumour marker concentrations. Retrospective SYSUCC cohort I (randomly assigned [7:3] to a training set and an internal validation set) and three prospective validation sets (SYSUCC cohort II [internal validation], HNCH cohort II [external validation], and CHSUMC cohort II [external validation]) were used in this step. Six machine-learning algorithms were compared (the least absolute shrinkage and selector operator regression, ridge regression, random forest, logistic regression, support vector machine, and neural network), and the best-performing algorithm was chosen as the final prediction model. Performance of SENSORS and the SENSORS-based diagnostic system was primarily assessed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). FINDINGS: Between Oct 1, 2017, and April 30, 2020, 1051 participants were included in the retrospective study. In the prospective diagnostic study, 924 participants were included from April 2, 2022, to Feb 2, 2023. Compared with ELISA (108·90 pg/mL) and ECLIA (41·79 pg/mL), SENSORS (243·03 fg/mL) showed 448 times and 172 times improvements, respectively. In the three retrospective validation sets, the SENSORS-based diagnostic system achieved AUCs of 0·95 (95% CI 0·90-0·99) in the SYSUCC internal validation set, 0·93 (0·89-0·97) in the HNCH external validation set, and 0·98 (0·97-1·00) in the CHSUMC external validation set, sensitivities of 87·1% (79·3-92·3), 98·6% (94·4-99·8), and 93·5% (88·1-96·7), and specificities of 88·9% (75·2-95·8), 74·6% (61·3-84·6), and 92·1% (81·7-97·0), respectively, successfully distinguishing between patients with oesophageal squamous cell carcinoma and healthy controls. Additionally, in three prospective validation cohorts, it yielded sensitivities of 90·9% (95% CI 86·1-94·2) for SYSUCC, 84·8% (76·1-90·8) for HNCH, and 95·2% (85·6-98·7) for CHSUMC. Of the six machine-learning algorithms compared, the random forest model showed the best performance. A feature selection step identified five features to have the highest performance to predictions (SCC, age, MMP13, CEA, and NSE) and a simplified random forest model using these five features further improved classification, achieving sensitivities of 98·2% (95% CI 93·2-99·7) in the internal validation set from retrospective SYSUCC cohort I, 94·1% (89·9-96·7) in SYSUCC prospective cohort II, 88·6% (80·5-93·7) in HNCH prospective cohort II, and 98·4% (90·2-99·9) in CHSUMC prospective cohort II. INTERPRETATION: The SENSORS system facilitates highly sensitive detection of oesophageal squamous cell carcinoma tumour biomarkers, overcoming the limitations of detecting low-abundance circulating proteins, and could substantially improve oesophageal squamous cell carcinoma diagnostics. This method could act as a minimally invasive screening tool, potentially reducing the need for unnecessary endoscopies. FUNDING: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Enterprises Joint Fund-Key Program of Guangdong Province. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Long-term mesoscale imaging of 3D intercellular dynamics across a mammalian organ.

A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irregularity, and phototoxicity pose great challenges, leading to an inevitable trade-off between volume size, resolution, speed, sample health, and system complexity. Here, we introduce a compact real-time, ultra-large-scale, high-resolution 3D mesoscope (RUSH3D), achieving uniform resolutions of 2.6 × 2.6 × 6 µm3 across a volume of 8,000 × 6,000 × 400 µm3 at 20 Hz with low phototoxicity. Through the integration of multiple computational imaging techniques, RUSH3D facilitates a 13-fold improvement in data throughput and an orders-of-magnitude reduction in system size and cost. With these advantages, we observed premovement neural activity and cross-day visual representational drift across the mouse cortex, the formation and progression of multiple germinal centers in mouse inguinal lymph nodes, and heterogeneous immune responses following traumatic brain injury-all at single-cell resolution, opening up a horizon for intravital mesoscale study of large-scale intercellular interactions at the organ level.

A review of Legionella transmission risk in built environments: sources, regulations, sampling, and detection.

The risk of Legionella transmission in built environments remains a significant concern. Legionella can spread within buildings through aerosol transmission, prompting the exploration of airborne transmission pathways and proposing corresponding prevention and control measures based on building characteristics. To this end, a comprehensive literature review on the transmission risk of Legionella in built environments was performed. Four electronic databases (PubMed, Web of Science, Google Scholar, and CNKI) were searched from inception to March 2024 for publications reporting the risk of Legionella transmission in built environments. Relevant articles and gray literature reports were hand-searched, and 96 studies were finally included. Legionella pollution comes from various sources, mainly originates in a variety of built environments in which human beings remain for extended periods. The sources, outbreaks, national standards, regulations, and monitoring techniques for Legionella in buildings are reviewed, in addition to increases in Legionella transmission risk due to poor maintenance of water systems and long-distance transmission events caused by aerosol characteristics. Air and water sampling using various analytical methods helps identify Legionella in the environment, recognize sources in the built environments, and control outbreaks. By comparing the standard regulations of national organizations globally, the authors further highlight gaps and deficiencies in Legionella surveillance in China. Such advancements offer essential insights and references for understanding and addressing Legionella transmission risk in the built environment, with the potential to contribute to safeguarding public health and building environment safety.

Introducing and Boosting Oxygen Vacancies within CoMn2O4 by Loading on Planar Clay Minerals for Efficient Peroxymonosulfate Activation.

CoMn2O4 (CMO) has been recognized as an effective peroxymonosulfate (PMS) activator; however, it still shows disadvantages such as limited reactive sites and metal leakage. Herein, an effective and environmentally friendly composite catalyst, CMO/Kln, was synthesized by anchoring CMO on kaolinite (Kln), a natural clay mineral with a special lamellar structure, to activate peroxymonosulfate (PMS) for the degradation of residue pharmaceuticals in water. The abundant hydroxyl groups located on the surface of Kln helped induce rich oxygen vacancies (OVs) into composite CMO/Kln, which not only acted as additional active sites but also accelerated working efficiency. In addition, compared with bare CMO, CMO/Kln showed lower crystallinity, and the adoption of the Kln substrate contributed to its structural stability with lower metal leaching after three rounds of reaction. The universal applicability of CMO/Kln was also verified by using three other pharmaceuticals as probes. This work shed light on the adoption of natural clay minerals in modifying CMO catalysts with promoted catalytic activity for the efficient and eco-friendly remediation of pharmaceuticals in wastewater.

Giant Intrauterine Mass Because of Puerperal Infection: A Case Report.

Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

Novel pretreatment nomograms based on pan-immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma.

Background: The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. Conclusions: The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.

Rare oxoisoaporphine alkaloids from Menispermum dauricum with potential anti-inflammatory activity.

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 µM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized.

Roles and challenges encountered by midwives in the management of postpartum haemorrhage following normal vaginal delivery: A scoping review.

AIMS: To establish a comprehensive understanding of the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of postpartum haemorrhage (PPH) following normal vaginal delivery. DESIGN: We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) recommendations. METHODS: We considered studies related to the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of PPH during vaginal delivery. We excluded guidelines, consensuses, abstracts of meetings and non-English language studies. Databases, including the Cochrane Library, PubMed, Web of Science, Ovid, Medline, Embase, JBI EBP and BIOSIS Previews, were searched on January 1, 2023, with no time limitations. RESULTS: We included 28 publications. Midwives play important roles in the prevention, diagnosis and management of postpartum haemorrhage during vaginal delivery. In the prevention of PPH, midwives' roles include identifying and managing high-risk factors, managing labour and implementing skin-to-skin contact. In the diagnosis of PPH, midwives' roles include early recognition and blood loss estimation. In the management of PPH, midwives are involved in mobilizing other professional team members, emergency management, investigating causes, enhancing uterine contractions, the repair of perineal tears, arranging transfers and preparation for surgical intervention. However, midwives face substantial challenges, including insufficient knowledge and skills, poor teamwork skills, insufficient resources and the need to deal with their negative emotions. Midwives must improve their knowledge, skills and teamwork abilities. Health care system managers and the government should give full support to midwives. Future research should focus on developing clinical practice guidelines for midwives for preventing, diagnosing and managing postpartum haemorrhage.

[Exploring the Spatial and Temporal Trajectories of Land Use Carbon Emissions and Influencing Factors in the Aksu River Basin from 1990 to 2020].

Land use changes lead to changes in the functions of different types of carbon sources and sinks, which are key sources of carbon emissions. The study of carbon emissions and its influencing factors in the Aksu River Basin from the perspective of land use change is of great importance for the promotion of integrated protection and restoration of mountains, water, forests, fields, lakes, grasslands, sand, and ice in the basin and to help achieve the goal of carbon peaking and carbon neutrality. Based on four periods of land use data and socio-economic data from 1990 to 2020, the total carbon emissions from land use were measured, and the spatial and temporal trajectories of carbon emissions and their influencing factors were explored. The results showed that:① from 1990 to 2020, arable land, forest land, construction land, and unused land showed a general increasing trend, whereas grasslands and water areas showed a decreasing trend. The spatial change in land use types was mainly characterized by the conversion of grasslands and unused land into arable land, and 83.58 % of the arable land conversion areas were concentrated in the southwest of Wensu, Aksu, and the northern part of Awat. ② The total net carbon emissions in the basin showed a continuous growth trend from 1990 to 2020, with a cumulative increase of 14.78×104 t. The increase in arable land was a key factor causing an increase in net carbon emissions in the basin. ③ The spatial distribution pattern of land use carbon emissions in the basin was high in the middle and low in the fourth, with significant changes in net carbon emissions mainly in the southern part of Wensu, Aksu, Awat, and Alaer. ④ Human activities had the strongest driving effect on land use carbon emissions, with their effects gradually increasing from east to west. The contribution of average annual temperature to land use carbon emissions was mainly concentrated in the eastern part of Aksu and the northern part of Awat, whereas average annual rainfall had a strong inhibitory effect on the northern part of Wensu and the western part of Aheqi.