Cross-species single-cell analysis uncovers the immunopathological mechanisms associated with IgA nephropathy progression.

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases.

Purpose: The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). Methods: From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Results: Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. Conclusion: In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

Investigation into the characteristics of electron beam-aged microplastics and adsorption behavior of dibutyl phthalate.

Microplastics are increasingly prevalent in the environment, and their ability to adsorb various organic additives, posing harm to organisms, has attracted growing attention. Currently, there are no effective methods to age microplastics, and there is limited discussion on the subsequent treatment of aged microplastics. This study focuses on micro polyethylene (PE) and employs electron beam technology for aging treatment, investigating the adsorption and leaching behavior between PE and dibutyl phthalate (DBP) before and after aging. Experimental results indicate that with increasing doses of electron beam irradiation, the surface microstructure of PE worsens, inducing the generation of oxygen-containing functional groups on the surface of polyethylene. Comparative evaluations between electron beam aging and existing methods show that electron beam technology surpasses existing aging methods, achieving a level of aging exceeding 0.7 within an extremely short period of one min at doses exceeding 350kGy. Adsorption experiments demonstrate that the adsorption between PE and DBP conforms to pseudo-second-order kinetics and the Freundlich model both before and after aging. The adsorption capacity of microplastics for DBP increases from 76.8 mg·g-1 to 167.0 mg·g-1 after treatment, exceeding that of conventional DBP adsorbents. Electron beam irradiation causes aging of microplastics mainly through the generation of ·OH, which lead to the formation of oxygen-containing functional groups on the microplastics' surface, thereby enhancing their adsorption capacity for DBP. This provides a new perspective for the degradation of aged microplastics and composite pollutants.

miR-92a-3p promotes pulmonary fibrosis progression by regulating KLF2-mediated endothelial-to-mesenchymal transition.

Pulmonary fibrosis (PF) is a chronic lung disease that has a poor prognosis and a serious impact on the quality of life of patients. Here, we investigated the potential role of miR-92a-3p in PF. The mRNA level of miR-92a-3p was significantly increased in both the lung tissues of bleomycin (BLM)--treated mice and pulmonary microvascular endothelial cells (PMVECs). Overexpressing miR-92a-3p increased the mRNA and protein levels of α­SMA, vimentin, and Col-1 but downregulated E-cadherin. Additionally, the protein and mRNA expression levels of KLF2 were significantly decreased in the lung tissues of BLM-treated mice, suggesting that KLF2 participated in the progression of BLM-induced PF. Downregulating miR-92a-3p upregulated the expression of KLF2 and inhibited the endothelial-to-mesenchymal transition (EndoMT) process, thus alleviating PF in vivo. Altogether, a miR-92a-3p deficiency could significantly reduce the development of myofibroblasts and ameliorate PF progression.

First-Principles Predictions of MoS2-WS2 In-Plane Heterostructures for Sensing Dissolved Gas Species in Oil-Immersed Transformers.

This work from first-principles insight uses a MoS2-WS2 in-plane heterostructure as a potential sensing material for detection of CO and C2H2, two typical dissolved gases in oil-immersed transformers, in order to evaluate the operation status. The adsorption performance of the MoS2-WS2 heterostructure upon two gas species is assessed via three adsorption sites and compared with isolated MoS2 and WS2. Results indicate that MoS2-WS2 performs with a much stronger binding force and charge-transfer for adsorptions of CO and C2H2 in comparison to the isolated counterpart, which gives rise to more obvious deformation in the electronic property of MoS2-WS2 as well as a much larger resistance-based sensing response. The recovery time of MoS2-WS2 for desorption of CO and C2H2 molecules is also appropriate to allow the reusability of such a sensor. The findings in this work uncover the admirable sensing potential of transition metal dichalcogenides (TMDs)-based heterostructures upon oil dissolved gases, which opens up a new way to explore novel 2D nanomaterials as resistive gas sensors for dissolved gas analysis in electrical oil-immersed transformers.

Radiomics analysis of pancreas based on dual-energy computed tomography for the detection of type 2 diabetes mellitus.

Objective: To utilize radiomics analysis on dual-energy CT images of the pancreas to establish a quantitative imaging biomarker for type 2 diabetes mellitus. Materials and methods: In this retrospective study, 78 participants (45 with type 2 diabetes mellitus, 33 without) underwent a dual energy CT exam. Pancreas regions were segmented automatically using a deep learning algorithm. From these regions, radiomics features were extracted. Additionally, 24 clinical features were collected for each patient. Both radiomics and clinical features were then selected using the least absolute shrinkage and selection operator (LASSO) technique and then build classifies with random forest (RF), support vector machines (SVM) and Logistic. Three models were built: one using radiomics features, one using clinical features, and a combined model. Results: Seven radiomic features were selected from the segmented pancreas regions, while eight clinical features were chosen from a pool of 24 using the LASSO method. These features were used to build a combined model, and its performance was evaluated using five-fold cross-validation. The best classifier type is Logistic and the reported area under the curve (AUC) values on the test dataset were 0.887 (0.73-1), 0.881 (0.715-1), and 0.922 (0.804-1) for the respective models. Conclusion: Radiomics analysis of the pancreas on dual-energy CT images offers potential as a quantitative imaging biomarker in the detection of type 2 diabetes mellitus.

Sorafenib plus TACE with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 78 patients with intermediate or advanced HCC who were treated at our centers between January 2018 and December 2021. 26 of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS: The mOS (22 vs. 10 months, P < 0.001) and mPFS (11 vs. 6 months, P = 0.008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumor progression. For grade I and II adverse events (AEs), the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the two groups (P > 0.05). CONCLUSION: Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE: 1.Subgroup analysis demonstrated TACE+ Sorafenib+ Camrelizumab could benefit HCC patients regardless of whether they had PVTT, BCLC B or C, or CHILD A or B；2.We reported the immunotherapy related adverse events (irAEs) occurred with a significant higher incidence in triple treatment, but all the adverse events are tolerable.

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and the risk of hepatocellular carcinoma: a nationwide cohort study.

Background/Aims: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. Methods: Information on study participants were derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. Association of evolutionary changes in MASLD status as assessed by fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using the multivariable-adjusted Cox proportional hazards regression. Results: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC than that of persistent non-MASLD. Conclusions: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

The role of the D-dimer to fibrinogen ratio in the classification of cardioembolism and atherosclerotic stroke.

BACKGROUND: The D-dimer-to-fibrinogen ratio (DFR) is a good indicator of thrombus activity in thrombotic diseases, but its clinical role in acute ischaemic stroke (AIS) patients with different etiologies has not been studied. We evaluated the diagnostic value of the DFR for different subtypes of AIS. METHODS: We conducted a single-center retrospective study of 269 patients with AIS who were referred to our stroke center within 4.5 h from Jan 2017 to Oct 2019. Coagulation data including DFRs were compared among the different stroke subtypes, and a separate retrospective validation sample was utilized to evaluate the prediction efficiency of the DFR for subtype diagnosis. RESULTS: A higher DFR was observed in patients with cardioembolism than in those with large artery atherosclerosis (LAA) (odds ratio (OR) per 0.1 increase of the DFR: 1.49 [1.01-2.18]) after we adjusted for vascular risk factors. The diagnostic value of the DFR for detecting cardioembolism (AUC = 0.722, 95 % CI = 0.623-0.820) exceeded that of isolated D-dimer or fibrinogen. The validation sample (n = 117) further supported the notion that a diagnosis of cardioembolism was more common in patients with a DFR > 0.11 (multivariable risk ratio = 3.11[1.33-7.31], P = 0.009). CONCLUSION: High DFRs were associated with cardioembolism in patients with AIS. The utilization of DFR can be beneficial for distinguishing a cardiac embolic source from atherosclerotic stroke.

"RNSP (Rannasangpei)" Rescued MK-801-induced Schizophrenia-like Behaviors in Mice via Oxidative Stress and BDNF-TrkB/Akt Pathway.

Schizophrenia (SCZ) is a complex, severe psychotic disorder that is highly persistent. Patients often cannot control their emotions and have delusions of victimization, world-weariness, and even suicide. Therefore, safer and more effective drugs are urgently needed. Rannasangpei (RNSP) from "the four medicine tantras" was used as a neuroprotective agent. The objective of this study was to investigate the effect and mechanism of RNSP on MK-801-induced SCZ in mice. Fifty C57BL/6J mice were randomly divided into a normal group, a model group, an RNSP group, a crocin (CRO) group, and an olanzapine (OLA) group, except for the normal group. The remaining mice were used to establish the MK-801-induced SCZ model. Changes in positive symptoms and cognitive impairment in mice before and after drug intervention were assessed by using the prepulse inhibition (PPI) test, Y-maze test (YMT), and open-field test (OFT). Intragastric administration of RNSP alleviated the symptoms of SCZ in SCZ mice, as demonstrated by the PPI, YMT, and OFT results. Compared with the model group, the first-line antipsychotic olanzapine reversed the anxiety-like phenotypes, hypermotility, and PPI deficits in the SCZ model mice. Further analysis revealed that RNSP reduced oxidative stress in SCZ model mice, as evidenced by increased superoxide dismutase (SOD) levels and decreased malondialdehyde (MDA) levels in the hippocampus, cortex, and blood of SCZ model mice. In our study, RNSP treatment restored the expression of brain-derived neurotrophic factor (BDNF), dopamine D2 receptor, p-Trkb, Akt/p-Akt, and doublecortin and inhibited the expression of IBA1 and Bax in the hippocampus of SCZ model mice. The polymerase chain reaction data indicated that RNSP treatment increased the expression of Bcl-2 and TGF-ß and decreased the expression of Bax, IL-1ß, and TNF-α in the brains of the model mice. Our results are the first to show that RNSP reverses SCZ-like behaviors in rodents (both positive symptoms and cognitive deficits) by reducing oxidative stress and activating the BDNF-TrkB/Akt pathway, suggesting that RNSP is a novel approach for treating SCZ.

Comprehensive review on lipid metabolism and RNA methylation: Biological mechanisms, perspectives and challenges.

Adipose tissue plays a crucial role in maintaining energy balance, regulating hormones, and promoting metabolic health. To address disorders related to obesity and develop effective therapies, it is essential to have a deep understanding of adipose tissue biology. In recent years, RNA methylation has emerged as a significant epigenetic modification involved in various cellular functions and metabolic pathways. Particularly in the realm of adipogenesis and lipid metabolism, extensive research is ongoing to uncover the mechanisms and functional importance of RNA methylation. Increasing evidence suggests that RNA methylation plays a regulatory role in adipocyte development, metabolism, and lipid utilization across different organs. This comprehensive review aims to provide an overview of common RNA methylation modifications, their occurrences, and regulatory mechanisms, focusing specifically on their intricate connections to fat metabolism. Additionally, we discuss the research methodologies used in studying RNA methylation and highlight relevant databases that can aid researchers in this rapidly advancing field.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

Therapeutic value of patent foramen ovale closure for drug-resistant epilepsy: A case series report.

OBJECTIVE: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. METHODS: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. RESULTS: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug-resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one-year follow-up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. SIGNIFICANCE: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug-resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. PLAIN LANGUAGE SUMMARY: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug-resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve.

Elevated CO2 exacerbates the risk of methylmercury exposure in consuming aquatic products: Evidence from a complex paddy wetland ecosystem.

Elevated CO2 levels and methylmercury (MeHg) pollution are important environmental issues faced across the globe. However, the impact of elevated CO2 on MeHg production and its biological utilization remains to be fully understood, particularly in realistic complex systems with biotic interactions. Here, a complete paddy wetland microcosm, namely, the rice-fish-snail co-culture system, was constructed to investigate the impacts of elevated CO2 (600 ppm) on MeHg formation, bioaccumulation, and possible health risks, in multiple environmental and biological media. The results revealed that elevated CO2 significantly increased MeHg concentrations in the overlying water, periphyton, snails and fish, by 135.5%, 66.9%, 45.5%, and 52.1%, respectively. A high MeHg concentration in periphyton, the main diet of snails and fish, was the key factor influencing the enhanced MeHg in aquatic products. Furthermore, elevated CO2 alleviated the carbon limitation in the overlying water and proliferated green algae, with subsequent changes in physico-chemical properties and nutrient concentrations in the overlying water. More algal-derived organic matter promoted an enriched abundance of Archaea-hgcA and Deltaproteobacteria-hgcA genes. This consequently increased the MeHg in the overlying water and food chain. However, MeHg concentrations in rice and soil did not increase under elevated CO2, nor did hgcA gene abundance in soil. The results reveal that elevated CO2 exacerbated the risk of MeHg intake from aquatic products in paddy wetland, indicating an intensified MeHg threat under future elevated CO2 levels.

The association between weight-adjusted-waist index and sarcopenia in adults: a population-based study.

This study aims to investigate the relationship between weight-adjusted-waist index (WWI), a new body index, and sarcopenia, while also assessing the potential of WWI as a tool for screening sarcopenic patients. The cross-sectional study involved adults who possessed complete data on WWI and appendicular skeletal muscle mass from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Surveys. Weighted multivariate regression and logistic regression analyses were employed to explore the independent relationship between WWI and sarcopenia. The study included 26,782 participants. The results showed that WWI demonstrated a positive correlation with sarcopenia risk. In the fully adjusted model, with each 1 unit increase in WWI, the risk of developing sarcopenia rose 14.55 times higher among males (OR: 14.55, 95% CI 12.33, 17.15) and 2.86 times higher among females (OR: 2.86, 95% CI 2.59, 3.15). The optimal cutoff values of WWI for sarcopenia were 11.26 cm/√kg for males and 11.39 cm/√kg for females. Individuals with a higher WWI have an increased risk of developing sarcopenia, and a high WWI functions as a risk factor for sarcopenia. Assessing WWI could assist in identifying individuals at risk of sarcopenia.

Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a major cause of incapacity and death, imposing a significant economic burden globally. Additionally, SAH is the third most prevalent form of stroke. Semaglutide affects oxidative stress, inflammation, and mitochondrial biogenesis. Specifically, the potential neuroprotective effect of semaglutide in SAH and its underlying mechanism is unclear. Accordingly, the present research intended to explore the neuroprotective effect of semaglutide in SAH and its potential molecular mechanisms. METHODS: We constructed a C57BL/6 mouse model of SAH. The parameters assessed were neuronal ferroptosis, neuroinflammatory cytokine levels, reactive oxygen species (ROS) levels, glutathione (GSH) and malondialdehyde (MDA) levels, brain water content, and neurological score. RESULTS: The results showed that the activation of semaglutide significantly increased neurological scores, relieved cerebral edema, decreased the levels of inflammatory cytokine nuclear factor kappa B, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, MDA, and ROS, and increased the levels of GSH. Suppression of SIRT1 reversed these effects, indicating that semaglutide activated SIRT1 to reduce neuroinflammation, ferroptosis, and neuronal cell death after SAH. Thus, the activation of the Nrf2/HO-1 signaling pathway contributes to the neuroprotective properties of semaglutide. CONCLUSIONS: Semaglutide can improve murine neurological outcomes and reduce neuronal damage against neuroinflammation and ferroptosis.

Peripheral 5-HT mediates GnIH-induced feeding behavior and energy metabolism disorder in chickens via the 5-HT2C receptor.

Gonadotropin-inhibitory hormone (GnIH) plays a critical role of reproduction in vertebrate since its discovery. Recently, a regulatory role of GnIH in appetite and the energy metabolism has emerged, despite its precise physiological mechanisms remain unknown. Thus, the present study evaluated the effects of a single or long-term GnIH treatments (administered via intraperitoneal injection) on the food intake, weight and glucolipid metabolism of chickens, while investigated the possible neuroendocrinology factors and its mechanism that involved in GnIH-induced obesity and glucolipid metabolism disorder. Our results showed that the intraperitoneal administration of GnIH to chickens resulted in marked body mass increased, hyperlipidemia, hyperglycemia and glucose intolerance. Subsequently, the results of metabolomics and pharmacological inhibition of 5-HT2C receptor studies revealed that blocked 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight and the levels of blood glucose and lipid, resulted in GnIH-induced hyperglycaemia, hyperlipidemia and hepatic lipid deposition even worse, suggesting that peripheral 5-HT via 5-HT2C receptor may act as a negative feedback regulator to interplay with GnIH and jointly homeostatic control of energy balance in chickens. Our present study provide evidence of the cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level and to propose a molecular basis for these interactions, suggesting that functional interaction between GnIH and 5-HT may open new avenues to understand the mechanism of neuroendocrine network involved in appetite and energy metabolism as well as provide a new therapeutic strategy to prevent obesity, diabetes and metabolic disorders.

A clinical-radiomics nomogram based on dual-layer spectral detector CT to predict cancer stage in pancreatic ductal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the efficacy of radiomics signatures derived from polyenergetic images (PEIs) and virtual monoenergetic images (VMIs) obtained through dual-layer spectral detector CT (DLCT). Moreover, it sought to develop a clinical-radiomics nomogram based on DLCT for predicting cancer stage (early stage: stage I-II, advanced stage: stage III-IV) in pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 173 patients histopathologically diagnosed with PDAC and who underwent contrast-enhanced DLCT were enrolled in this study. Among them, 49 were in the early stage, and 124 were in the advanced stage. Patients were randomly categorized into training (n = 122) and test (n = 51) cohorts at a 7:3 ratio. Radiomics features were extracted from PEIs and 40-keV VMIs were reconstructed at both arterial and portal venous phases. Radiomics signatures were constructed based on both PEIs and 40-keV VMIs. A radiomics nomogram was developed by integrating the 40-keV VMI-based radiomics signature with selected clinical predictors. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). RESULTS: The PEI-based radiomics signature demonstrated satisfactory diagnostic efficacy, with the areas under the ROC curves (AUCs) of 0.92 in both the training and test cohorts. The optimal radiomics signature was based on 40-keV VMIs, with AUCs of 0.96 and 0.94 in the training and test cohorts. The nomogram, which integrated a 40-keV VMI-based radiomics signature with two clinical parameters (tumour diameter and normalized iodine density at the portal venous phase), demonstrated promising calibration and discrimination in both the training and test cohorts (0.97 and 0.91, respectively). DCA indicated that the clinical-radiomics nomogram provided the most significant clinical benefit. CONCLUSIONS: The radiomics signature derived from 40-keV VMI and the clinical-radiomics nomogram based on DLCT both exhibited exceptional performance in distinguishing early from advanced stages in PDAC, aiding clinical decision-making for patients with this condition.

From field soil sampling to watershed model: Upscaling by integrating information entropy and interpolation method.

Soil property data plays a crucial role in watershed hydrology and non-point source (H/NPS) modeling, but how to improve modeling accuracy with affordable soil samplings and the effects of sampling information on H/NPS modeling remains to be further explored. In this study, the number of sampling points and soil properties were optimized by the information entropy and the spatial interpolation method. Then the sampled properties were parameterized and the effects of different parameterization schemes on H/NPS modeling were tested using the Soil and Water Assessment Tool (SWAT). The results indicated that the required sampling points increased successively for soil bulk density (SOL_BD), soil saturated hydraulic conductivity (SOL_K) and soil available water capacity (SOL_AWC). Compared to the traditional database (Harmonized world soil database), the NSE and R2 performance by new scheme increased by 22.8% and 10.5%, respectively. The entropy-based optimization reduced the sampling points by 13.2%, indicating a more cost-effective scheme. Compared to hydrological simulation, sampled properties showed greater effects on NPS modeling, especially for nitrogen. This proposed method/framework can be generalized to other watersheds by upscaling field soil sampling information to the watershed scale, thus improving H/NPS simulation.

Continuous veno-venous hemofiltration with oXiris hemofilters for the treatment of Fournier's gangrene: A case report series.

Background: Fournier's gangrene (FG) is a severe form of necrotizing fasciitis primarily caused by gram-negative bacteria. FG can rapidly progress to septic shock, resulting in high mortality rates. In the past, the management of the inflammatory response caused by gram-negative bacteria has been limited. Continuous Veno-Venous Hemofiltration with oXiris hemofilters (oXiris-CVVH) has shown promise in adsorbing inflammatory factors and endotoxins, making it an attractive approach for treating FG. This study aims to provide insights into the characteristics of patients with FG and septic shock who have been successfully treated using oXiris-CVVH, based on a series of patient cases. Results: This study presents the management of 4 cases in the intensive care units of a tertiary hospital in southern China. The use of oXiris-CVVH in patients with septic shock and FG yielded valuable practical insights. Conclusion: Based on the experience gained from these 4 cases, the utilization of oXiris-CVVH demonstrated potential in reducing the Sequential Organ Failure Assessment (SOFA) score, improving prognosis, and effectively lowering the levels of lactic acid and procalcitonin (PCT) in the blood. Additionally, it facilitated a reduction in the dosage of noradrenaline. Therefore, oXiris-CVVH should be considered as an adjunctive therapy in the treatment of patients with FG and septic shock.