Defect-Enabled Superior Negative Thermal Quenching in Palmierite Ba9La(VO4)7:Eu3+ for WLED In Situ Temperature Measuring.

Negative thermal quenching (NTQ) of the phosphors is critically important for both scientific research and practical applications, but the design of efficient NTQ phosphors is still a challenging task. Herein, we report a new strategy for developing NTQ materials by cation-vacancy engineering. Specifically, a new color-tunable Ba9La1-x(VO4):xEu3+ (BLVO:xEu3+) phosphor with abundant intrinsic cation vacancy was developed, exhibiting superior NTQ behavior under 365 nm excitation. The NTQ performance can be modulated via adjusting Eu3+ doping levels, and the emission intensity of Eu3+ ions in the BLVO:0.20Eu3+ phosphor increased by 275% at 473 K compared to room temperature. Furthermore, the reported material emitting bright white light under 365 nm excitation was well-suited for use in white light-emitting diode (WLED) phosphor and fluorescent temperature sensors, exhibiting outstanding color-rendering index (90.1) in lighting and high sensitivity (Sa = 11.83% K-1, Sr = 2.33% K-1) in temperature detecting. Lastly, the operating temperature of WLED at different currents can be monitored and displayed in real time through emission spectroscopy. All of the results demonstrated that the designed NTQ BLVO:xEu3+ can be used as a single-phase white phosphor and optical thermometry. This work provides a fresh perspective for designing high-efficient NTQ phosphors and expands the application of phosphors in WLED in situ temperature detection.

Functional activity, functional connectivity and complex network biomarkers of progressive hyposmia Parkinson's disease with no cognitive impairment: evidences from resting-state fMRI study.

Background: Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson's disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson's disease still remain elusive. Methods: This study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics. Results: We discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores. Conclusion: Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients.

Allicin Ameliorated High-glucose Peritoneal Dialysis Solution-induced Peritoneal Fibrosis in Rats via the JAK2/STAT3 Signaling Pathway.

Peritoneal fibrosis (PF) is one of the most serious complications of peritoneal dialysis (PD) and is the greatest obstacle to the clinical application of PD. Chinese herbal monomers have been effective in the prevention and treatment of PF. The aim of this study was to observe the effect of allicin on PF in rats induced by high glucose and to investigate its molecular mechanism of action. A rat model of PF was established by using a 4.25% glucose-based standard peritoneal dialysis solution. The degree of peritoneal pathological damage was assessed by Hematoxylin and eosin (H&E) staining. Peritoneal collagen deposition was detected by Masson's trichrome staining. The levels of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß) and monocyte chemoattractant protein-1 (MCP-1) in the serum were measured by Enzyme Linked Immunosorbent Assay (ELISA). The expression levels of TGF-ß, α-smooth muscle actin (α-SMA) and collagen I were examined by western blotting and immunohistochemistry. The protein expression levels and mRNA levels of E-cadherin, N-cadherin, vimentin, janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in peritoneal tissue were determined by western blotting and qRT-PCR. TGF-ß1 stimulated human peritoneal mesothelial cells (HPMCs), and the cells were treated with allicin and the JAK2/STAT3 pathway activator colivelin alone or in combination. A cell counting kit-8 (CCK-8) assay was used to measure cell viability. The role of JAK2/STAT3 in the effects of allicin was confirmed via in vitro mechanistic research by western blotting, wound healing assays and Transwell assays. Allicin relieves the inflammatory response by downregulating the levels of IL-1ß, IL-6, MCP-1 and TNF-α. Furthermore, allicin decreased the expression of TGF-ß, α-SMA and collagen I. Allicin also alleviated epithelial-to-mesenchymal transition (EMT), as specifically manifested by increased E-cadherin and reduced N-cadherin and vimentin. Further studies revealed that allicin reduced the protein levels of JAK2, STAT3, p-JAK2, and p-STAT3. The results of the cellular experiments verified the above results. The ability of allicin to inhibit fibrosis and the EMT process was significantly attenuated after HPMCs were treated with colivelin. Taken together, these findings suggest that allicin inhibits inflammation and EMT, thereby improving PF, and this protective effect may be achieved by inhibiting the JAK2/STAT3 signaling pathway.

On the contribution of atmospheric reactive nitrogen deposition to nitrogen burden in a eutrophic Lake in eastern China.

Although it has been demonstrated that atmospheric reactive nitrogen (i.e., Nr mainly including NH3, NH4+, NOx, NO3- and etc.) deposition has substantial impacts on nitrogen pools in remote and/or sensitive lakes, there is a scarcity of systematic evaluations regarding the impact on nitrogen burden in eutrophic lakes with riverine input as primary nitrogen source. Utilizing a regional atmospheric chemical transport model, combined with observation-based estimates of atmospheric nitrogen deposition fluxes and riverine nitrogen inputs, we investigate the contribution of atmospheric Nr deposition to the fifth largest freshwater lake located in eastern China, i.e., the Chaohu Lake which is facing frequent outbreaks of algal bloom. The results indicate that in the studied year of 2022, riverine total nitrogen (TN) input to the lake was 11553.3 t N yr-1 and atmospheric TN deposition was 2326.0 t N yr-1. For Nr species which are directly available for the biosphere supporting algae and plant growth, riverine NH4+ input was 1856.1 t N yr-1 and atmospheric NHx (NH3 and NH4+) deposition was 824.5 t N yr-1. The latter accounts for 30.8% of total NHx input to the lake. For NOy (HNO3 and NO3-), riverine NO3- input was estimated as 2621.7 t N yr-1, while atmospheric NOy deposition was 629.3 t N yr-1, accounting for 19.4%. In all, atmospheric Nr deposition accounts for 24.5 % of total Nr input to the lake. Our results suggest that even in regions with dense human activities with primary riverine N input, atmospheric deposition of Nr could also contribute significantly to the bio-available nitrogen in lake systems, and addressing eutrophication in Lake Chaohu and other eutrophic lakes will also need to consider the influence of atmospheric Nr deposition which is related to NH3 and NOx (i.e., NO + NO2, the precursor of NOy) emissions, in addition to the mitigation of riverine N input.

Label-Aware Dual Graph Neural Networks for Multi-Label Fundus Image Classification.

Fundus disease is a complex and universal disease involving a variety of pathologies. Its early diagnosis using fundus images can effectively prevent further diseases and provide targeted treatment plans for patients. Recent deep learning models for classification of this disease are gradually emerging as a critical research field, which is attracting widespread attention. However, in practice, most of the existing methods only focus on local visual cues of a single image, and ignore the underlying explicit interaction similarity between subjects and correlation information among pathologies in fundus diseases. In this paper, we propose a novel label-aware dual graph neural networks for multi-label fundus image classification that consists of population-based graph representation learning and pathology-based graph representation learning modules. Specifically, we first construct a population-based graph by integrating image features and non-image information to learn patient's representations by incorporating associations between subjects. Then, we represent pathologies as a sparse graph where its nodes are associated with pathology-based feature vectors and the edges correspond to probability of the co-occurrence of labels to generate a set of classifier scores by the propagation of multi-layer graph information. Finally, our model can adaptively recalibrate multi-label outputs. Detailed experiments and analysis of our results show the effectiveness of our method compared with state-of-the-art multi-label fundus image classification methods.

Comparison of the safety and efficacy of three superficial skin closure methods for multi-layer wound closure in total knee arthroplasty: a multicenter, prospective, randomized controlled trial.

BACKGROUND: Good wound healing is critical to infection prophylaxis and satisfactory rehabilitation in Total Knee Arthroplasty (TKA). Currently, two techniques, i.e., barbed continuous subcuticular suture without skin adhesive or combined use skin adhesive (n-butyl-2) are being used for superficial wound closure of TKA. While a new skin adhesive (2-octyl) with self-adhesive mesh has been employed as an alternative to conventional surgical skin closure in TKA, its superiority, especially in reducing wound complications and improving wound cosmetic outcomes has not been investigated. This study aimed to compare 2-octyl, n-butyl-2, and no skin adhesive in terms of safety and efficacy in TKA superficial wound closure. METHODS: We conducted a multicenter, prospective, randomized controlled study in 105 patients undergoing primary TKA between May 2022 and October 2023. Each patient's knee was randomized to receive 2-octyl, n-butyl-2, or no skin adhesive skin closure with all using barbed continuous sutures in deep tissue. Wounds were followed 1, 3, 5 days, 2, 6 weeks, and 3 months after surgery. Wound discharge, complications, cosmetic outcomes, patient satisfaction, and wound-related costs were compared among these three methods. RESULTS: Wound discharge was less in 2-octyl group and n-butyl-2 group than in non-adhesive group at 1 day, with the discharge only being less in 2-octyl group than in the non-adhesive group at day 3 and day 5 days (P < 0.05). There was no statistical difference in the incidence of other wound complications among the groups (P > 0.05). The 2-octyl group achieved better cosmetic effects than the other two groups in 6 weeks and 3 months (P < 0.05). Compared to the non-adhesive group, 2-octyl group scored higher in overall patient satisfaction score in 2 weeks and incurred lower costs (P < 0.05). CONCLUSIONS: Skin closure in TKA using 2-octyl adhesive material showed superiority when compared to no skin adhesive or n-butyl-2, in reducing wound discharge, improving the cosmetic outcomes, without increasing wound complications. In addition, the use of 2-octyl yielded better patient satisfaction and also was less costly compared to no skin adhesive. Our study exhibited that 2-octyl was a safe and effective wound closure technique for patients undergoing TKA. TRIAL REGISTRATION: This study has been registered at Clinical Trials. Gov (No. ChiCTR210046442).

Graph Neural Networks With Adaptive Confidence Discrimination.

Graph neural networks (GNNs) have demonstrated remarkable success for semisupervised node classification. However, these GNNs are still limited to the conventionally semisupervised framework and cannot fully leverage the potential value of large numbers of unlabeled samples. The pseudolabeling method in semisupervised learning (SSL) is widely recognized because it can clearly leverage unlabeled samples. Nevertheless, the existing pseudolabeling methods usually utilize a fixed threshold for all classes and only use a portion of unlabeled samples (ones with high prediction confidence), which leads to class imbalance and low data utilization. To solve these problems, we propose GNNs with adaptive confidence discrimination (ACDGNN) to fully utilize unlabeled samples for facilitating semisupervised node classification. Specifically, an adaptive confidence discrimination module is designed to divide all unlabeled nodes into two subsets by comparing their confidence scores with the adaptive confidence threshold at each training epoch. Then, different constraint strategies for two subset nodes are employed. Unlabeled nodes with high confidence are used to iteratively expand the label set, while ones with low confidence learn discriminative features by applying contrastive learning. Validated by extensive experiments, the proposed ACDGNN delivers significant accuracy gains over the previous SOTAs: an average improvement of 2.0% on all datasets and 5.7% on the Flickr dataset in particular.

Anal canal duplication with heterotopic gastric mucosa and anal stenosis: first case report and literature review.

Introduction: Anal canal duplication (ACD) is a rare entity of gastrointestinal duplication that may be asymptomatic or present complications, such as abscess, fistulae, or malignant changes. The diagnosis and rational management of ACD still need to be clarified. Case presentation: We present a case of an 18-month-old girl with intractable perianal erosion and painful bowel movements for one year, and chronic constipation for six months. Fistulography revealed a tubular structure (3 cm in length), located posterior to the native anal canal. Mucosectomy was performed through a perineal approach combined with a coccigeal approach, and the postoperative course was uneventful. The pathological findings confirmed the diagnosis of ACD with heterotopic gastric mucosa, a rare combination that has not been described in the literature before. A literature search was conducted on the Medline database for studies reporting ACD in children. The study pool consisted of 77 cases of ACD from 32 studies, including the present case. According to our case report and in line with the literature, 43 cases (55.84%) were incidentally found; the most frequent symptom was constipation (14.29%), followed by painful anal mass or sacral pain (10.39%), and recurrent fistula (7.79%). Coexisting diseases were observed in 31 patients (40.26%), including 19 (24.68%) cases associated with presacral masses. Surgical management was employed in 73 patients (94.81%). ACD excision was performed in 47 patients (64.38%), combined with presacral mass resection or coccygectomy in 19 cases (26.03%). Conclusion: Preoperative imaging, including fistulography, ultrasonography, and magnetic resonance imaging, can provide useful information, especially for screening its associated anomalies. To prevent potential complications, surgical removal of ACD and associated anomalies is recommended. Mucosectomy may be one of the most effective surgical options for ACD due to its excellent functional outcome.

The impact of a lung-protective ventilation mode using transpulmonary driving pressure titrated positive end-expiratory pressure on the prognosis of patients with acute respiratory distress syndrome.

OBJECTIVE: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS). METHODS: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients. RESULTS: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999). CONCLUSION: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

Composite dietary antioxidant index is associated with renal anemia: a cross-sectional study.

An increasing evidence suggested that chronic kidney disease (CKD) is closely related to oxidative stress, and dietary antioxidant intake can serve as a primary preventive measure for CKD. However, the relationship between composite dietary antioxidant index (CDAI) and renal anemia is not well understood. We postulated that elevated CDAI levels would be inversely related to a higher likelihood of renal anemia. The standardized calculation of CDAI was performed to investigate the relationship between them by a binary regression model. A non-linear relationship was examined through restricted cubic spline curves, and then pinpointed the inflection point. Subgroup analysis was then used to assess the robustness of the model. Finally 5880 participants were included in the study and a notable correlation between CDAI and renal anemia was found (P < 0.0001). In the multivariate linear regression model with adjustment for all confounding variables, the odds ratio (OR) and 95% confidence interval (CI) was 0.96 (0.94, 0.98; P < 0.0001), A non-linear relationship between CDAI and renal anemia was explored through restricted cubic splines, with a inflection at 6.005. Before the inflection point, for each unit rise in CDAI, the prevalence of renal anemia decreased by 5.7%. Subgroup analysis showed no statistically significant differences in interactions between any subgroups (P > 0.05). Our findings indicated a non-linear negative correlation between CDAI and renal anemia. The causal relationship still needs to be further clarified through large-scale prospective studies.

Multi-omics analysis reveals a crosstalk between ferroptosis and peroxisomes on steatotic graft failure after liver transplantation.

To identify the mechanism underlying macrosteatosis (MaS)-related graft failure (GF) in liver transplantation (LT) by multi-omics network analysis. The transcriptome and metabolome were assayed in graft and recipient plasma in discovery (n = 68) and validation (n = 89) cohorts. Differentially expressed molecules were identified by MaS and GF status. Transcriptional regulatory networks were generated to explore the mechanism for MaS-related inferior post-transplant prognosis. The differentially expressed molecules associated with MaS and GF were enriched in ferroptosis and peroxisome-related pathways. Core features of MaS-related GF were presented on decreased transferrin and impaired anti-oxidative capacity dependent upon dysregulation of transcription factors hepatocyte nuclear factor 4A (HNF4A) and hypoxia-inducible factor 1A (HIF1A). Furthermore, miR-362-3p and miR-299-5p inhibited transferrin and HIF1A expression, respectively. Lower M2 macrophages but higher memory CD4 T cells were observed in MaS-related GF cases. These results were validated in clinical specimens and cellular models. Systemic analysis of multi-omics data depicted a panorama of biological pathways deregulated in MaS-related GF. Transcriptional regulatory networks centered on transferrin and anti-oxidant responses were associated with poor MaS graft quality, qualifying as potential targets to improve prognosis of patients after LT.

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study.

OBJECTIVE: Heterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients. METHODS: We conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed. RESULTS: The study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel's diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel's diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient's age, the lesion site and size, and coexisting diseases. CONCLUSIONS: Only one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel's diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

Identification and treatment of intestinal malrotation with midgut volvulus in childhood: a multicenter retrospective study.

Background: Intestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children. Methods: Clinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed. Results: The mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p < 0.05 and p < 0.01, respectively. The incidence of abnormal ultrasound (US) findings was 97.30% and 100%, respectively, and the sensitivities of the upper gastrointestinal series were 84.21% and 87.5%, respectively. Sixty-six (88%) patients had midgut volvulus, including in utero volvulus (two patients) and irreversible intestinal ischemia (four patients). Most neonates (89.29%) underwent open Ladd's procedure with a shorter operative time (p < 0.01). Reoperation was performed for postoperative complications (four patients) or missed comorbidities (two patients). Conclusions: Non-bilious vomiting was the initial symptom in >10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.

A dual strategy of Na+/vacancy disorder and high Na to construct a P2-type cathode for high-stability sodium-ion batteries.

P2-type layered oxides are widely regarded as highly promising contenders for cathode materials in sodium-ion batteries. However, the occurrence of severe reactive phase transitions hinders satisfactory cycling stability and rate performance, thereby imposing limitations on their practical application. Here we prepared P2-type Na0.75Ni0.23Mg0.1Mn0.67O2 cathode materials using the agar gel approach. The use of agar reduces the synthesis time significantly, and the high Na content enhances the stability of the structure and contributes to its capacity. Meanwhile, the introduction of electrochemically inactive Mg ions into sodium layers not only disrupts the Na+/vacancy ordering, but also increases the spacing between sodium layers, thus reducing the diffusion barrier for sodium ions. The dual modification strategy led to excellent stability of Na0.75Ni0.23Mg0.1Mn0.67O2 with 94% capacity retention after 100 cycles at 1C. This work provides new insights into the design of sodium-ion cathode materials.

Non-traumatic osteonecrosis of the femoral head induced by steroid and alcohol exposure is associated with intestinal flora alterations and metabolomic profiles.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. METHODS: Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. RESULTS: High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. CONCLUSIONS: Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Topology Optimization Method of Stamping Structures Based on the Directional Density Field.

The stamping process produces thin-walled structures that, in general, have uniform wall thickness and no enclosed cavity. However, it is difficult to satisfy the above geometric requirements with the current density-based topology optimization method, since configuring the related geometric constraints is challenging. In order to solve this problem, a topology optimization method for stamping structures based on a directional density field is proposed. Specifically, the directional density field is developed to enable the adding and removing of materials only along the stamping direction, so as to avoid internal voids and concave features. The geometric control for uniform wall thickness is realized by tuning the truncation threshold of the Heaviside projection that processes the directional density field into the 0-1 binary field. At the same time, a calibrated filter radius of the truncation thresholds will facilitate the drawing angle control of the stamping ribs. The effectiveness of the established method has been verified by a number of numerical case studies. Results show that the proposed method can perform topology optimization for stamping structures with tunable uniform thickness and drawing angle control of the ribs. No internal voids or undercuts appear in the results. The results also disclose that a constant truncation threshold increment does not guarantee uniform wall thickness, and varying the threshold increments through surface offset and polynomial fitting is necessary.

Multi-parametric investigations on the effects of vascular disrupting agents based on a platform of chorioallantoic membrane of chick embryos.

Background: Vascular disrupting agents (VDAs) are known to specifically target preexisting tumoural vasculature. However, systemic side effects as safety or toxicity issues have been reported from clinical trials, which call for further preclinical investigations. The purpose is to gain insights into their non-specific off-targeting effects on normal vasculature and provide clues for exploring underlying molecular mechanisms. Methods: Based on a recently introduced platform consisting laser speckle contrast imaging (LSCI), chick embryo chorioallantoic membrane (CAM), and assisted deep learning techniques, for evaluation of vasoactive medicines, hemodynamics on embryonic day 12 under constant intravascular infusion of two VDAs were qualitatively observed and quantitatively measured in real time for 30 min. Blood perfusion, vessel diameter, vessel density, and vessel total length were further analyzed and compared between blank control and medicines dose groups by using multi-factor analysis of variance (ANOVA) analysis with factorial interactions. Conventional histopathology and fluorescent immunohistochemistry (FIHC) assays for endothelial cytoskeleton including ß-tubulin and F-actin were qualitatively demonstrated, quantitatively analyzed and further correlated with hemodynamic and vascular parameters. Results: The normal vasculature was systemically negatively affected by VDAs with statistical significance (P<0.0001), as evidenced by four positively correlated parameters, which can explain the side-effects observed among clinical patients. Such effects appeared to be dose dependent (P<0.0001). FIHC assays qualitatively and quantitatively verified the results and exposed molecular mechanisms. Conclusions: LSCI-CAM platform combining with deep learning technique proves useful in preclinical evaluations of vasoactive medications. Such new evidences provide new reference to clinical practice.

Anti-papillary thyroid carcinoma effects of dioscorea bulbifera L. through ferroptosis and the PI3K/AKT pathway based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate persists. Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, has been historically used for thyroid-related disorders. However, its therapeutic effects and mechanisms of action on PTC remain unclear. AIM OF THE STUDY: To explore the potential therapeutic effects, principal active components, and molecular mechanisms of DBL in the treatment of PTC through network pharmacology and molecular docking, with experimental validation conducted to corroborate these findings. MATERIALS AND METHODS: The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was utilized as a systematic tool for collecting and screening the phytochemical components of DBL, and for establishing associations between these components and molecular targets. Based on this, network data was visually processed using Cytoscape software (version 3.8.0). Concurrently, precise molecular docking studies of the principal active components of DBL and their corresponding targets were conducted using Autodock software. Additionally, PTC-related genes were selected through the GeneCards and GEO databases. We further employed the DAVID bioinformatics resources to conduct comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the intersecting genes between DBL and PTC. These analyses aid in predicting the potential therapeutic actions of DBL on PTC and its mechanisms of action. To validate these findings, corresponding in vitro experimental studies were also conducted. RESULTS: In this investigation, 14 bioactive compounds of DBL and 195 corresponding molecular targets were identified, with 127 common targets shared between DBL and PTC. Molecular docking revealed strong binding affinities between major bioactive compounds and target proteins. GO enrichment analysis unveiled key processes involved in DBL's action. KEGG analysis highlighted DBL's modulation of the PI3K/AKT signaling pathway. Experimental outcomes demonstrated DBL's potential in inhibiting PTC cell proliferation and migration, suppressing PI3K/AKT pathway activation, and promoting ferroptosis. CONCLUSION: In conclusion, DBL offers a multifaceted therapeutic approach for PTC, targeting multiple molecular entities and influencing diverse biological pathways. Network pharmacology and molecular docking shed light on DBL's potential utility in PTC treatment, substantiated by experimental validation. This study contributes valuable insights into using DBL as a promising therapeutic agent for PTC management.

NiCo-compounds inside and outside N-doped carbon nanotubes to construct a double-enhanced hierarchical structure for high energy density supercapacitors.

Attaining a high energy density that aligns with practical application requirements is a crucial indicator in the advancement of supercapacitors. In this paper, a hybrid hierarchical electrode structure of N-doped carbon nanotube (NCNT) spheres encapsulated with NiCo-Se nanoparticles (NPs) and coated with nickel-cobalt layered double hydroxide (NiCo-LDH) multilayer nanosheets was successfully synthesized on a nickel foam (NF) substrate. The self-supporting strategy enables nickel-cobalt Prussian blue analogues (Ni-Co PBAs) to be directly attached to the NF surface, which results in fluffy NCNTs with a high length-diameter ratio and considerable yield and greatly enhances the conductivity of the electrode material. The synergistic interaction between the dual transition metal compounds inside and outside the NCNTs enables the hybrid electrode material to achieve an impressive specific capacity of 1899 F g-1 (211.0 mA h g-1) at 1 A g-1. The asymmetric supercapacitor (ASC) exhibits an excellent energy density of 57.6 W h kg-1 at a power density of 798 W kg-1. This study not only provides an attractive strategy for obtaining CNTs with excellent properties from Ni-Co PBA and synthesizing hybrid electrodes with efficient synergistic effects, but also achieves a high energy density that aligns with the practical application demands of supercapacitors.

Comprehensive analysis of the gene expression profile of the male and female BTBR mice with diabetic nephropathy.

Comprehensive insight into the gender-based gene expression-related omics data in a rodent model of diabetic nephropathy (DN) is scarce. In the present study, the gender-based genes regulating different pathways involved in the progression of DN were explored through an unbiased RNA sequence of kidneys from BTBR mice with DN. We identified 17,739 and 17,981 genes in male and female DN mice; 1121 and 655 genes were expressed differentially (DEGs, differentially expressed genes) in male and female DN mice; both genders displayed only 195 DEGs. In the male DN mice, the number of upregulated genes was nearly the same as that of the down-regulated genes. In contrast, the number of upregulated genes was lesser than that of the down-regulated genes in the female DN mice, manifesting a remarkable gender disparity during the progression of DN in this animal model. Gene Ontology (GO) and KEGG-enriched results showed that most of these DEGs were related to the critical biological processes, including metabolic pathways, natural oxidation, bile secretion, and PPAR signaling; all are highly associated with DN. Notably, the DEGs significantly enriched for steroid hormone biosynthesis pathway were identified in both genders; the number of DEGs increased was 22 in male DN mice and 14 in female DN mice. Specifically, the Ugt1a10, Akr1c12, and Akr1c14 were upregulated in both genders. Interestingly, the Hsd11b1 gene was upregulated in female DN mice but downregulated in male DN mice. These results suggest that a significant gender-based variance in the gene expression occurs during the progression of DN and may be playing a role in the advancement of DN in the BTBR mouse model.