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Guo Jinlin,1,* Song Shaohui,2,* Zhang Wenjun,3 Cai Xinfeng4 1Department of Pharmacy, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China; 2Department of Pharmacy, The Maternal and Child Health Hospital of Dadukou District of Chongqing City, Chongqing, People’s Republic of China; 3Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Pharmacy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cai Xinfeng, Shanxi Province Cancer Hospital, Taiyuan, Shanxi, 030012, People’s Republic of China, Tel +86-18835167718, Email caixinfeng5236@126.comAbstract: We report a case of co-infection with Nocardia farcinica, Pneumocystis jirovecii, and Aspergillus fumigatus due to tooth extraction in a mildly immunosuppressed patient. This patient did not respond well to a meropenem-based regimen, and the number of lesions was significantly reduced after switching to imipenem. The patient’s trough concentration was insufficient when using conventional doses of voriconazole for the treatment of pulmonary aspergillosis. After adding omeprazole, the concentration reached standard levels and symptoms improved. The patient eventually made a full recovery.Keywords: Aspergillus fumigatus, interaction, intracranial infection, Nocardia farcinica, Pneumocystis jirovecii, voriconazole

Introduction: This experimental in vitro study aimed to identify and characterize hypothermia-associated coagulopathy and to compare changes in mild to severe hypothermia with the quantitative measurement of rotational thromboelastometry (ROTEM) and multiple-electrode aggregometry (MULTIPLATE).Methods: Whole blood samples from 18 healthy volunteers were analyzed at the target temperatures of 37, 32, 24, 18, and 13.7°C with ROTEM (ExTEM, InTEM and FibTEM) and MULTIPLATE using the arachidonic acid 0.5 mM (ASPI), thrombin receptor-activating peptide-6 32 µM (TRAP) and adenosine diphosphate 6.4 µM (ADP) tests at the corresponding incubating temperatures for coagulation assessment.Results: Compared to baseline (37°C) values ROTEM measurements of clotting time (CT) was prolonged by 98% (at 18°C), clot formation time (CFT) was prolonged by 205% and the alpha angle dropped to 76% at 13.7°C (p < 0.001). At 24.0°C CT was prolonged by 56% and CFT by 53%. Maximum clot firmness was only slightly reduced by ≤2% at 13.7°C. Platelet function measured by MULTIPLATE was reduced with decreasing temperature (p < 0.001): AUC at 13.7°C −96% (ADP), −92% (ASPI) and −91% (TRAP).Conclusion: Hypothermia impairs coagulation by prolonging coagulation clotting time and by decreasing the velocity of clot formation in ROTEM measurements. MULTIPLATE testing confirms a linear decrease in platelet function with decreasing temperatures, but ROTEM fails to adequately detect hypothermia induced impairment of platelets.

IntroductionHypothermia has notable effects on platelets, platelet function, fibrinogen, and coagulation factors. Common laboratory techniques cannot identify those effects, because blood samples are usually warmed to 37°C before analysis and do not fully reflect the in vivo situation. Multiple aspects of the pathophysiological changes in humoral and cellular coagulation remain obscure. This in vitro experimental study aimed to compare the measurements of thromboelastometry (TEM), multiple-electrode aggregometry (MEA) and Real Time Live Confocal Imaging for the purpose of identifying and characterizing hypothermia-associated coagulopathy.MethodsBlood samples were drawn from 18 healthy volunteers and incubated for 30 min before being analyzed at the target temperatures (37, 32, 24, 18, and 13.7°C). At each temperature thromboelastometry and multiple-electrode aggregometry were measured. Real Time Live Confocal Imaging was performed at 4, 24, and 37°C. The images obtained by Real Time Live Confocal Imaging were compared with the functional results of thromboelastometry and multiple-electrode aggregometry.ResultsThromboelastometry standard parameters were impaired at temperatures below baseline 37°C (ANOVA overall effect, p < 0.001): clotting time was prolonged by 27% at 13.7°C and by 60% at 18°C (p < 0.044); clot formation time was prolonged by 157% (p < 0.001). A reduction in platelet function with decreasing temperatures was observed (p < 0.001); the area under the curve at 13.7°C was reduced by 96% (ADP test), 92% (ASPI test), and 91% (TRAP test) of the baseline values. Temperature-associated changes in coagulation were visualized with Real Time Live Confocal Imaging. Molecular changes such as the temperature-associated decrease in the fibrin network are paralleled by cellular effects like the lesser activity of the platelets as a result of decreased temperature. The maximum clot firmness (MCF) in TEM only changed slightly within the temperature range tested.ConclusionThe inhibitory effects of temperature on clot formation were visualized with Real Time Live Confocal Microscopy and compared with standard point-of-care testing. Inhibition of clotting factors and impaired platelet function are probably a result of hypothermia-induced impairment of thrombin. Measurement of MCF in TEM does not fully concur with Real Time Live Confocal Microscopy or MEA in hypothermia.

Abstract To improve the scientific accuracy and precision of children’s physical fitness evaluations, this study proposes a model that combines self-organizing maps (SOM) neural networks with cluster analysis. Existing evaluation methods often rely on traditional, single statistical analyses, which struggle to handle the complexity of high-dimensional, nonlinear data, resulting in a lack of precision and personalization. This study uses the SOM neural network to reduce the dimensionality of high-dimensional health data. Moreover, it integrates cluster analysis to categorize and analyze key physical fitness attributes, such as strength, flexibility, and endurance. Experimental results show that the proposed optimized model outperforms comparison models such as T-distributed stochastic neighbor embedding, density peak clustering, and deep embedded clustering in terms of performance. The accuracy for the strength dimension reaches 0.934, the F1 score is 0.862, and the area under the curve of receiver operating characteristic is 0.944. The silhouette coefficients for cluster analysis in strength, flexibility, and endurance dimensions are 0.655, 0.559, and 0.601, respectively, demonstrating good intra-class and inter-class distances. The proposed model enhances the comprehensive analysis of children’s physical fitness and provides a scientific basis for personalized health interventions, making an important contribution to research in this field.

Abstract Sepsis is one of the leading causes of death among seriously ill patients worldwide, affecting more than 30 million people annually and accounting for 1–2% of hospitalizations. By analyzing gene expression omnibus (GEO) data set, our team explored the relationship between m6A methylation gene and poor prognosis of sepsis. The purpose of this present study is to examine new detection markers for patients with poor prognosis, provide theoretical basis for timely intervention and improve the survival rate of patients. First, GSE54514 transcriptome data were extracted from the GEO database 31 patients with sepsis related death and 72 sepsis survivors. Key genes were screened from differentially expressed genes (DEGs), least absolute shrinkage and selection operator (LSAAO) and random forest (RF). And then, METTL3, WTAP and RBM15 were further verified by quantitative reverse transcription PCR (qRT-PCR). The constructed nomogram model showed high accuracy in predicting death. These three genes are mainly involved in chemokine signaling pathway, differentiation of monocytes and T cells, and phagocytosis of immune cells. The analysis showed that a high m6A score subtype is linked to lower immunosuppression and higher survival rates in clinical samples, suggesting better immune responses and outcomes for these patients. Finally, the protective effect of METTL3 in sepsis was demonstrated in mouse sepsis model applied with METTL3 inhibitor, by conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) and hematoxylin–eosin (HE) staining. In conclusion, these findings provide potential biomarkers and targets for early precision diagnosis and treatment.

Abstract Background Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear. Methods The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice. Results BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments. Conclusion BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.

Abstract Background Mixed granulocytic asthma (MGA) is usually associated with poor response to corticosteroid therapy and a high risk of severe asthma. Cathepsin S (CTSS) has been found to play an important role in various inflammatory diseases. This study was aimed to investigate the role of CTSS in MGA. Methods Induced sputum was obtained from healthy subjects and asthma patients. Two murine models of MGA were established using either TDI (toluene diisocyanate) alone or OVA emulsified in CFA. LY3000328, a specific antagonist of CTSS, was therapeutically given to BALB/c mice after airway challenge with TDI or OVA. The effects of recombinant CTSS was tested in vivo, and Akt inhibition was used to explore a possible mechanism for CTSS-induced airway inflammation. Results MGA patients have a significant higher sputum CTSS level than the health and subjects with other inflammatory phenotypes, which was positively correlated with sputum level of soluble E-cadherin (sE-cadherin), sputum neutrophils, FeNO, FEF25-75% and glucocorticoid dosage. Allergen exposure markedly increased CTSS level and pharmacological antagonism of CTSS with LY3000328 decreased airway hyperresponsiveness, airway neutrophil accumulation, as well as the release of IL-17 and sE-cadherin in murine models of MGA, yet had no effects on eosinophilic inflammation nor type 2 inflammatory cytokines (IL-4 and IL-5). In addition, intratracheal instillation of recombinant CTSS leads to neutrophil recruitment and overproduction of sE-cadherin in the lung tissues, which could be attenuated by inhibition of Akt signaling. Conclusion Our data suggested that CTSS contributes to airway neutrophilic inflammation in MGA through an Akt-dependent pathway.

Abstract To achieve scalable universal quantum computing, we need to implement a universal set of logical gates fault-tolerantly, for which the main difficulty lies with non-Clifford gates. We demonstrate that several characteristic features of the reconfigurable atom array platform are inherently well-suited for addressing this key challenge, potentially leading to significant advantages in fidelity and efficiency. Specifically, we consider a series of different strategies, including magic state distillation, concatenated code array, and fault-tolerant logical multi-controlled-Z gates, leveraging key platform features such as nonlocal connectivity, parallel gate action, collective mobility, and native multi-controlled-Z gates. Our analysis provides valuable insights into the efficient experimental realization of logical gates, serving as a guide for the full-cycle demonstration of fault-tolerant quantum computation with reconfigurable atom arrays.

Abstract Background To develop and validate an interpretable machine learning model based on intratumoral and peritumoral radiomics combined with clinicoradiological features and metabolic information from magnetic resonance spectroscopy (MRS), to predict clinically significant prostate cancer (csPCa, Gleason score ≥ 3 + 4) and avoid unnecessary biopsies. Methods This study retrospectively analyzed 350 patients with suspicious prostate lesions from our institution who underwent 3.0 Tesla multiparametric magnetic resonance imaging (mpMRI) prior to biopsy (training set, n = 191, testing set, n = 83, and a temporal validation set, n = 76). Intratumoral and peritumoral volumes of interest (VOIintra, VOIperi)) were manually segmented by experienced radiologists on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Radiomic features were extracted separately from the VOIintra and VOIperi. After feature selection via the recursive feature elimination (RFE) algorithm, intratumoral radiomic score (intra-rad-score) and peritumoral radiomic score (peri-rad-score) were constructed. The clinical model, MRS model, and combined model integrating radiomic, clinicoradiological and metabolic features were constructed via the eXtreme Gradient Boosting (XGBoost) algorithm. The predictive performance of the models was evaluated in both the training and testing sets using receiver operating characteristic (ROC) curve analysis. SHapley Additive exPlanations (SHAP) analysis was applied to the combined model to visualize and interpret the prediction process. Results A total of 350 patients were included, comprising 173 patients with csPCa (49.4%) and 177 patients with non-csPCa (50.6%). The intra-rad-score and peri-rad-score were constructed via 10 and 16 radiomic features. The combined model demonstrated the highest AUC, accuracy, F1 score, sensitivity, and specificity in the testing set (0.968, 0.928, 0.927, 0.932, and 0.923, respectively) and in the temporal validation set (0.940, 0.895, 0.890, 0.923, and 0.875, respectively). SHAP analysis revealed that the intra-rad-score, PSAD, peri-rad-score, and PI-RADS score were the most important predictors of the combined model. Conclusion We developed and validated a robust machine learning model incorporating intratumoral and peritumoral radiomic features, along with clinicoradiological and metabolic parameters, to accurately identify csPCa. The prediction process was visualized via SHAP analysis to facilitate clinical decision- making.

To investigate and elucidate the influencing factors and laws of double-roll coating ratio (CR) for papermaking reconstituted tobacco and to assess the effectiveness of CR in characterizing the finished product's hot water soluble (HWS) content, base sheet (BS) specimens of reconstituted tobacco with varying bone-dry basis weights and moisture contents were prepared. These sheets were then coated with different physical indices of coating liquids using a small double-roll coater at different sheet speeds. Subsequently, the CR and HWS content of the finished product were analyzed. The results showed that when the viscosity of the coating liquid was > 280 mPa·s, the moisture content of the BS should be maintained between 18% and 22%, and the speed of the BS should be > 120 m/min; when the viscosity of the coating liquid is < 280 mPa·s, the moisture content of the BS should be maintained between 14% and 18%, and the speed of the BS should be > 120 m/min, so that higher HWS can be obtained in finished products. The bone-dry basis weight of the BS should be kept between 40 and 60 g/m2. The suspension solid content of coating liquid should be

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoantibody-triggered central nervous system (CNS) demyelinating disease that primarily affects the spinal cord, optic nerves and brainstem. Among the first responders to CNS injury, microglia are prominent players that drive NMOSD lesion formation. However, the key molecular switches controlling the detrimental activity of microglia in NMOSD are poorly understood. CD22 governs the activity of innate and adaptive immunity. In this study, we investigated to what extent and by what mechanisms CD22 may modulate microglial activity, neuroinflammation and CNS lesion formation. Methods To determine the expression profile of CD22 in NMOSD, we performed single-cell sequencing and flow cytometry analysis of immune cells from human peripheral blood. We investigated the potential effects and mechanisms of CD22 blockade on microglial activity, leukocyte infiltration and CNS demyelination in a mouse model of NMOSD induced by injection of NMOSD patient serum-derived AQP4-IgG and human complement. Results Single-cell sequencing and flow cytometry analysis revealed that CD22 was expressed in B cells, neutrophils, monocytes and microglia-derived exosomes in human peripheral blood from NMOSD patients and controls (n = 5 per group). In a mouse model of NMOSD, CD22 was expressed in B cells, neutrophils, monocytes and microglia (n = 8 per group). In NMOSD mice, CD22 blockade significantly increased the number of CNS lesions, astrocyte loss and demyelination, accompanied by increased inflammatory activity and phagocytosis in microglia. Furthermore, the detrimental effects of CD22 blockade were significantly alleviated in NMOSD mice subjected to depletion of microglia or Gr-1+ myeloid cells, suggesting the involvement of microglia and peripheral Gr-1+ myeloid cells. Additionally, CD22 blockade also led to significantly reduced phosphorylation of SYK and GSK3β in NMOSD. Notably, the detrimental effects of CD22 blockade were greatly diminished in NMOSD mice receiving the phosphorylated SYK inhibitor R406. Conclusions Our findings revealed a previously unrecognized role of CD22 as a key molecular switch that governs the detrimental effects of microglia and Gr-1+ myeloid cells in NMOSD, which paves the way for the future design of immune therapies for NMOSD. Graphical abstract

Abstract Background Dietary cholesterol promotes metabolic dysfunction-associated steatohepatitis (MASH), with hepatic macrophages central to disease pathology. However, the mechanisms by which cholesterol-loaded macrophages influence MASH remain unclear. Methods In this study, mice were fed a cholesterol-rich choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Hepatic cholesterol levels, inflammatory markers, and pro-inflammatory macrophage polarization were assessed. In vitro studies examined the impact of cholesterol on macrophage polarization, identifying 7-dehydrocholesterol reductase (DHCR7) as a key cholesterol- and inflammation-responsive enzyme. DHCR7 expression in macrophages from MASH patients and model mice was evaluated. Functional studies involving in vitro knockdown and overexpression experiments, were complemented using myeloid-specific DHCR7 knockout mice. RNA sequencing was performed on liver tissues from wild-type and DHCR7 knockout mice to identify affected signaling pathways. Results CDAHFD-fed mice exhibited local cholesterol accumulation and a pro-inflammatory macrophage phenotype in the liver. Cholesterol overload in vitro promoted M1 polarization and liver inflammation, reversible by simvastatin. DHCR7 expression, responded to cholesterol and polarization state, was downregulated in M1-polarized and hepatic macrophages from MASH patients and mice. DHCR7 suppression promoted pro-inflammatory phenotype, while its overexpression showed anti-inflammatory effects. Myeloid-specific DHCR7 deficiency in CDAHFD-fed mice worsened liver inflammation and pro-inflammatory macrophage infiltration. RNA sequencing identified the phosphoinositide 3-kinase (PI3K) pathway in DHCR7-regulated effects, with DHCR7-PI3K axis activation mitigating cholesterol-driven inflammation. Conclusions These findings unveil novel mechanistic insights into MASH pathogenesis, suggesting targeting macrophage-specific DHCR7 activation may offer a promising therapeutic strategy for MASH.

Abstract Cold stress has a significantly negative effect on the growth, development, and yield of rice. However, the genetic basis for the differences in the cold tolerance of Xian/indica and Geng/japonica rice seedlings is still largely unknown. In this study, an RIL population was generated by crossing of the cold-tolerant japonica variety Nipponbare and the cold-sensitive indica variety WD16343 for BSA-seq analysis, and a major cold tolerance QTL qCTS11 was identified on chromosome 11. This locus was narrowed to the 584 kb region through fine mapping. Sequence alignment and expression analysis identified the cloned gene COLD11 and a novel cold-related gene OsCTS11. According to the reported functional variation of COLD11, Nipponbare (TCG + 3GCG)×2 presented more GCG repeats in the 1st exon than WD16343 (TCG + 3GCG), partially explaining the difference in cold tolerance between the parents. OsCTS11, encoding a stress enhanced protein based on phylogenetic analysis, was strongly induced by cold stress and located in the chloroplast and the nucleus. oscts11-mutant lines generated via CRISPR/Cas9 system improved the cold tolerance of rice seedlings. Our study not only reveals novel genetic loci associated with cold tolerance, but also provides potentially valuable gene resources for the cultivation of cold-tolerant rice.

Abstract The 2023–2024 El Niño has raised widespread concern in scientific and public communities. Here, using latest observational reanalysis, we show that this event matured with two distinct spatial peaks of sea surface temperature anomaly in the equatorial central and eastern Pacific, respectively. Like other double-peaked El Niños, the central Pacific sea surface temperature peaked in winter due to zonal advective and thermocline feedbacks. However, the eastern counterpart matured asynchronously in autumn and then stopped growing. This peculiar behavior results primarily from a cooling zonal advection by the anomalous westward current in the eastern Pacific during the autumn of 2023, which is associated with the local wind-driven sea surface height meridional concavity. We further propose that the relatively stronger and more eastward-displaced autumn precipitation in the Pacific intertropical convergence zone in 2023, compared to other double-peaked El Niños, is the primary cause of this distinct wind and sea surface height pattern.

Abstract Early screening methods for the thyroid gland include palpation and imaging. Although palpation is relatively simple, its effectiveness in detecting early clinical signs of the thyroid gland may be limited, especially in children, due to the shorter thyroid growth time. Therefore, this constitutes a crucial foundational work. However, accurately determining the location and size of the thyroid gland in children is a challenging task. Accuracy depends on the experience of the ultrasound operator in current clinical practice, leading to subjective results. Even among experts, there is poor agreement on thyroid identification. In addition, the effective use of ultrasound machines also relies on the experience of the ultrasound operator in current clinical practice. In order to extract sufficient texture information from pediatric thyroid ultrasound images while reducing the computational complexity and number of parameters, this paper designs a novel U-Net-based network called DC-Contrast U-Net, which aims to achieve better segmentation performance with lower complexity in medical image segmentation. The results show that compared with other U-Net-related segmentation models, the proposed DC-Contrast U-Net model achieves higher segmentation accuracy while improving the inference speed, making it a promising candidate for deployment in medical edge devices in clinical applications in the future.

Abstract Pantropical climate interactions across ocean basins operate on a wide range of timescales and can improve the accuracy of climate predictions. Here, we show in observations that Central Pacific (CP) El Niño-like sea surface temperature (SST) anomalies have coevolved with tropical South Atlantic SST anomalies on a quasi-decadal (~10-year) timescale over the past seven decades. During the austral autumn–winter season, decadal warm SSTs in the tropical CP effectively induce tropical SST cooling in the South Atlantic, mainly by strengthening the South Atlantic subtropical anticyclone via an extratropical atmospheric wave teleconnection in the southern hemisphere. Partially coupled pacemaker simulations corroborate the observational findings, indicating that tropical CP decadal SSTs play a primary pacing role, while Atlantic feedback is of secondary importance throughout the study period. Our results suggest that the tropical CP could be an important source of decadal predictability for tropical South Atlantic SST and the surrounding climate.

In present study a method that enables users to dynamically insert the forest plot into a web page was presented. In this method, I created a Javascript module for generating and inserting a HTML table, including an entry function and two sub-functions. When the user applies it, copy these functions together with the table mark into the web page location where the forest plot is to be inserted. The web page will generate the forest plot by passing in parameters and calling the entry function in the user's own Javascript module. The full Javascript codes were given for free uses of web developers.

In-situ experimental observation cannot be an effective method in the impact process of metal cavitation erosion, and the impact damage energy prediction theory has not been established based on a detailed mathematical and physical model. Research has shown that the metal material can be regarded as a sensor to reflect the impact parameters. Soft metal materials such as industrial pure copper with a single α-phase microstructure can be a suitable sensor to detect cavitation erosion effects, revealing the impact behaviors of the cavitation jet through the depth, width and spatial distribution of cavitation pits on the surface. In this scenario, volume loss of cavitation pits on a macro/mesoscale are obtained by three-dimensional surface measurement. A coupled fluid-solid simulation model calculating the impact damage energy on a macro/mesoscale is established based on the Smoothed Particle Hydrodynamics (SPH) and the Crystal Plasticity Finite Element Method (CPFEM). Python programming is used to set the trajectory of SPH particles to determine the macro cavitation flow field. IFEM methods were used to construct the prediction theory of cavitation impact energy in a relatively simple exponential equation, establishing the quantitative relationship between cavitation impact damage energy and measured volume of cavitation pits. Compared with conventional measurement and simulation, the present multiscale approaches are assumed as a further step advancement towards calculating the impact damage energy of cavitation water jet.

Abstract Two-dimensional (2D) materials, as adsorbents, have garnered great attention in removing heavy metal ions (HMIs) from drinking water due to their extensive exposed adsorption sites. Nevertheless, there remains a paucity of experimental research to remarkably unlock their adsorption capabilities and fully elucidate their adsorption mechanisms. In this work, exceptional lead ion (Pb2+) (a common HMI) removal capacity (up to 758 mg g−1) is achieved using our synthesized metallic 1T/1T′ phase 2D transition metal dichalcogenide (TMD, including MoS2, WS2, TaS2, and TiS2) nanosheets, which hold tremendous activated S chemisorption sites. The residual Pb2+ concentration can be reduced from 2 mg L−1 to 2 μg L−1 within 0.5 min, meeting the drinking water standards following World Health Organization guideline (Pb2+ concentrations

Abstract Background Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. Methods Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells. Results Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. Conclusion This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Abstract Introduction Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection, especially in children and older people. However, no effective treatment is currently available. Type I interferons (IFNs) are a group of cytokines that help regulate the activity of the immune system. GB05, human IFNα1b inhalation solution, was developed under US Food and Drug Administration (FDA) standard guidelines to combat RSV infection. This randomized, double-blind, placebo-controlled, dose-escalation phase I trial evaluated the safety, tolerability, and pharmacokinetics of nebulized GB05. Methods A total of 35 eligible healthy Chinese adult volunteers were enrolled in this study. In the single ascending dose (SAD) study, volunteers were randomized into 0.2, 0.6, 1.2, and 1.8 million IU of GB05 or placebo. In the multiple ascending dose (MAD) study, volunteers received 1.2 or 1.8 million IU of GB05 or placebo for four consecutive days. Safety, tolerability, immunogenicity, and plasma pharmacokinetics were assessed for all groups. Results All adverse events were mild or moderate and resolved spontaneously. The most common adverse event was decreased white blood cell count (8.6% in SAD and 10% in MAD). No serious adverse events, deaths, or adverse events that reached the termination criteria occurred during the study. In SAD, the maximum concentration and area under the curve increased across the dose range of 1.2–1.8 million IU in a non-linear relationship. The maximum plasma concentration after GB05 nebulization (1.06 IU/ml in the 1.8 million IU group) reflected a low concentration in the blood, suggesting a better lung uptake of GB05 and reduced incidence or risks of adverse events. In MAD, a steady state was reached after continuous administrations of twice daily for 3 days. Conclusions Overall, nebulized GB05 exhibited satisfactory safety, tolerability, and favorable pharmacokinetic (PK) profiles in healthy adult volunteers, supporting further clinical investigation in patients infected with respiratory syncytial virus. Clinical Trial Registration ClinicalTrials.gov Identifier NCT06277167.

Marine biofouling seriously affects human marine exploitation and transportation activities, to which marine antifouling (AF) coatings are considered to be the most cost-effective solution. Since the mid-20th century, human beings have dedicated their efforts on developing AF coatings with long cycle and high performance, leading to a large number of non-target organisms' distortion, death and marine environmental pollution. Polydimethylsiloxane (PDMS), is considered as one of the representative environment-friendly AF materials thanks to its non-toxic, hydrophobic, low surface energy and AF properties. However, PDMS AF coatings are prone to mechanical damage, weak adhesion strength to substrate, and poor static AF effect, which seriously restrict their use in the ocean. The rapid development of various nanomaterials provides an opportunity to enhance and improve the mechanical properties and antifouling properties of PDMS coating by embedding nanomaterials. Based on our research background and the problems faced in our laboratory, this article presents an overview of the current progress in the fields of PDMS composite coatings enhanced by different nanomaterials, with the discussion focused on the advantages and main bottlenecks currently encountered in this field. Finally, we propose an outlook, hoping to provide fundamental guidance for the development of marine AF field.

BackgroundBerberine (BBR) is widely used to treat gastrointestinal diseases. However, the pharmacological mechanism of action of BBR in anti-chronic atrophic gastritis (CAG) remains unclear. This study aimed to investigate the mechanism of action of BBR in CAG by integration of molecular biology and multi-omics studies strategy.MethodsThe CAG model was established by alternating drinking water of 0.1% ammonia and 20 mmol/L sodium deoxycholate, accompanied by an irregular diet. Serum biochemical indices including PGI, PGII, GAS-17, IL-6, IL-1β, and TNF-α were analyzed. HE and AB-PAS staining were employed to assess pathological damage in gastric tissue. The underlying molecular mechanism of BBR in CAG treatment was explored via the integration of network pharmacology, transcriptomics, widely targeted metabolomics and intestinal flora analysis. Finally, relevant key targets and pathway were verified.ResultsThe results showed that BBR exerted therapeutic effects in improving CAG via alleviating inflammation response, maintaining the gastric mucosal barrier’s integrity and repairing gastric mucosal tissues. Network pharmacology showed that the treatment of CAG by BBR mainly involved in inflammatory response, apoptosis, angiogenesis and metabolic processes. Furthermore, 234 different expression genes were identified in the gastric tissue transcriptome, which were mainly involved in biological processes such as cell adhesion, angiogenesis, apoptosis, cell migration and lipids metabolism by regulating the MAPK signaling pathway. Metabolomics results showed that 125 differential metabolites were also identified, while the pathways were mainly involved in D-glutamine and D-glutamate metabolism, and tyrosine metabolism, etc. Integrating transcriptomics and metabolomics analyses indicated that BBR directly regulated Carnitine C3:0, LPC (0:0/20:3), L-Glutamic Acid and FFA (15:0) by acting on SLC25A20, PNLIPRP1, PLA2G4C, GSR, GFPT2, GCLM, CTPS1, ACSL1, ACOT4 and ACOT2. 16S rRNA sequencing revealed that BBR could restore the balance of gut microbiota dysbiosis by significantly regulating the relative abundance of unclassified_Muribaculaceae and Lactobacillus_johnsonii.ConclusionThis study demonstrated that BBR alleviates CAG through the regulation of the MAPK signaling pathway, metabolic disorders and gut microbiota dysbiosis, thereby revealing the complex mechanism of BBR in relation to alleviating CAG from multiple levels and perspectives.

Bisphenol A (BPA) is an exogenous endocrine disruptor in the environmental context, garnering attention for its harmful effects on the nervous system function and behavior. Research indicates that being exposed to BPA may result in anxiety-like behavior and impairment in cognitive function. Enriched environment (EE) is beneficial to improve cognitive behavior, but whether EE can improve BPA-induced behavioral impairment is still unclear. This research explored the possible pathways through which EE alleviates anxiety-like behavior and cognitive impairment in mice exposed to BPA. Except for the control mice, all mice received BPA treatment. After BPA treatment, some mice were housed normally, some housed with EE, and some were given NMDA and AMPA receptor agonists. Our research revealed that exposure to BPA results in anxiety-like behavior in open field and elevated-plus maze experiments. Additionally, spatial and learning memory cognitive impairments were observed in Y-maze and water maze tests. Furthermore, exposure to BPA led to a decrease in both the density and maturity of dendritic spines, as well as a reduction in neurite length and branch numbers. PSD-95, GluA1, and NR2A expression were down-regulated, and excitatory synaptic transmission was decreased. However, EE treatment increased dendrite spine density and maturity, up-regulated PSD-95, GluA1and NR2A expression, enhanced excitatory synaptic transmission, and relieved anxiety-like behavior and cognitive impairment in BPA mice. Furthermore, administering NMDA or AMPA receptor agonists to BPA mice led to an increase in dendritic spine density and maturity, a rise in mEPSC amplitude, as well as a restoration of anxiety-like behavior and cognitive deficits induced by BPA. The findings of this study provide proof that EE has a neuroprotective effect in reducing anxiety-related behavior and cognitive decline caused by BPA.

The growth and development of faults are driven by repetitive earthquakes, which accumulate displacement and extend rupture lengths. This process changes fault morphology, resulting in surface ruptures that are preserved in the geomorphology as displaced landforms. High-resolution geomorphic data enable the precise acquisition of these displaced landforms, facilitating detailed analysis of slip distributions along faults and offering quantitative constraints on the growth and rupture history of faults. In this study, an airborne light detection and ranging (LiDAR) system was employed to obtain 0.5-m resolution geomorphic data >500 m long on both sides of the Luoshan Fault on the northeastern Tibetan Plateau. By interpreting and distinguishing different geomorphic markers, we identified and measured 436 right-lateral offsets along the Luoshan Fault. Based on statistical analysis methods, we determined that there were six strong earthquakes within 10 m of the cumulative displacement along the Luoshan Fault. Except for the latest event, the other five strong events showed regular displacement increments of approximately 1.9 m, revealing a strong earthquake pattern of approximate characteristic slip. The different cumulative displacement distributions correspond to various stages of fault growth. The growth pattern of the Luoshan Fault evolves from fault tip propagation and linkage (Events 1–5) to a mode of growth with a constant fault length but increased cumulative displacement (Event 6). Based on the displacement distribution along the Luoshan Fault, the northern segment is more likely to experience earthquake events, with magnitudes ranging from Mw 6.84 to 7.12.

Real-time non-line-of-sight imaging is crucial for practical applications. Among existing methods, transient methods present the best visual reconstruction ability. However, most transient methods require a long acquisition time, thus failing to deal with real-time imaging tasks. Here, we provide a dual optical coupling model to describe the spatiotemporal propagation of photons in free space, then propose an efficient non-confocal transformation algorithm and establish a non-confocal time-to-space boundary migration model. Based on these, a scan-free boundary migration method is proposed. The data acquisition speed of the method can reach 151 fps, which is ∼7 times faster than the current fastest data acquisition method, while the overall imaging speed can also reach 19 fps. The background stability brought by fast scan-free acquisition makes the method suitable for dynamic scenes. In addition, the high robustness of the model to noise makes the method have the capability of non-line-of-sight imaging in outdoor environments during the daytime. To further enhance the practicality of this method in real-world scenarios, we exploit the statistical prior and propose a plug-in-and-play super-resolution method to extract higher spatial resolution signals, reducing the detector array requirement from 32 × 32 to 8 × 8 without compromising imaging quality, thus reducing the device expense of detectors.

BackgroundThe main goals of surgery for fistula-in-ano are to completely resolve the condition and maintain optimal anal function. Effective management of the internal opening during and proper postoperative drainage of the intersphincter plane are crucial for achieving successful outcomes. This study evaluated the clinical efficacy of a novel sphincter-sparing technique for treating high transsphincteric anal fistula (HTAF).MethodsThis prospective study included 55 patients with HTAF who underwent closed trans-intersphincteric fistulotomy (CTiF) between July 2021 and April 2022 at our institution. Preoperative anorectal magnetic resonance imaging was performed for all patients. The primary outcome measures assessed the rate of fistula healing while the secondary outcome measures evaluated healing time, Cleveland Clinic Florida fecal incontinence score (CCF-FIS), 11-point visual analog scale (VAS) pain score and postoperative complications.ResultsWe included 55 patients with HTAF in this study. During a mean follow-up period of 9.3 months, CTiF achieved a healing rate of 90.91% (50/55). The mean time to recovery was 7.09 ± 1.94 weeks. Four (7.27%) patients developed postoperative urinary retention. At the 6-month follow-up, the CCF-FIS and VAS score were 0 [(0,0) range, 0–3] and 0 [(0,1); range, 0–4], respectively. Two patients with recurrent HTAF recovered after treatment with a transanal opening of intersphincteric space procedure, and three recovered after seton placement.ConclusionsCTiF is a promising and effective sphincter-sparing technique for treating HTAF. To confirm long-term outcomes, larger sample size prospective randomized controlled trials are required.

The flavor profiles of cherries cultivated in greenhouse and those grown in open fields show significant variations, however, the underlying flavor-contributing factors remain unidentified. Hence, a joint investigation with widely targeted metabolomics analysis, volatile fingerprint analysis, and descriptive sensory analysis for the Russia 8 and Tieton cherry cultivars was conducted using UPLC-MS/MS and GC × GC-TOFMS to clarify the flavor differences of open-air and greenhouse-grown cherries. The study found that open-air cultivation could lead to the accumulation of non-volatile flavor substances and prompted appearance of higher acidity, astringency, plum-like flavor, and fresh herb notes; most of differential metabolites were significantly positively correlated with astringency, plum-like flavor and bitterness. Through correlation analysis and path analysis, potential flavor components and key important pathways contributing to flavor disparities were provided, and light intensity, soil moisture content, temperature and humidity were inferred as the main factors affecting the flavor profiles of open-air and greenhouse-grown cherries.

BackgroundUnilateral pulmonary artery discontinuity (UPAD) is a rare fetal abnormality, for which a prenatal ultrasonographic diagnosis remains challenging. We report a case of left pulmonary artery discontinuity in association with Taussig–Bing syndrome, which has rarely been reported in the literature thus far.Case presentationA pregnant woman with a fetus with congenital heart disease (CHD) at 23 weeks gestation was referred to our center. She denied any familial history of genetic disorders in either spouse, and non-invasive prenatal testing (NIPT) also showed a low risk of CHD for the fetus. An ultrasound examination revealed a complex cardiac malformation indicative of left pulmonary artery discontinuity originating from the ductus arteriosus with Taussig–Bing syndrome. The family eventually chose to terminate the pregnancy and agreed to an autopsy, which confirmed that the prenatal echocardiographic diagnosis was correct. In addition, in this report, we review and analyze 17 reported cases of prenatal echocardiographic diagnoses of UPAD.ConclusionsUPAD is characterized by discontinuity between the proximal and distal pulmonary arteries, along with a ductal origin of the distal pulmonary artery. A discontinuous pulmonary artery originating from the ductus can be detected on prenatal sonography using ultrasound technology. The aim is to detect malformations earlier and carry out the necessary intervention measures as soon as possible.

The research of short-chain fluorocarbon surfactants is crucial in effectively and environmentally extinguishing petrochemical fires. In this study, a short-chain fluorocarbon surfactant named 2H,2H-perfluorooctanoic acid sodium salt (PFH-CA) was synthesized, and then characterized its chemical structure, thermal stability, surface activity, and foam property. Subsequently, PFH-CA was compounded with hydrocarbon surfactants including sodium dodecyl sulfate (SDS), dodecyl trimethyl ammonium chloride (DTAC), and N,N-dimethyldodecylamine-N-oxid (OB-2) at different molar ratios. The surface tension, interaction parameters, and foam property of the PFH-CA/hydrocarbon surfactant compounding systems were investigated. The analysis indicates that PFH-CA exhibits excellent surface activity and thermal stability concomitant with poor foam property. Introducing SDS, DTAC, and OB-2 enhances the foam performance and reduces the consumption of PFH-CA through synergistic interactions. Especially, PFH-CA/DTAC (1:4) system possesses the strongest interactions and the best performance, with critical micelle concentration (CMC) and surface tension at CMC (γCMC) of 0.11 mmol/L and 20.90 mN/m, respectively. When concentration of PFH-CA exceeds 0.5 mmol/L, the foaming ability and foam stability stabilize at 30 cm and 90 %, respectively. The enhanced performance of PFH-CA/DTAC system is attributed to the electrostatic attraction between anionic and cationic surfactants, which facilitates the formation of micelles, subsequently leading to better surface activity and foam properties.

The submerged cavitation water jet (SCWJ) is a promising technology for removing solid propellant from old solid rocket engines and recycling them. In this study, the feasibility of using SCWJ to break solid propellant is investigated. The structure of the cavitation cloud was captured by a high-speed camera and then analyzed using the Proper Orthogonal Decomposition (POD) and Frame Difference Method (FDM) method for exploring the unsteady characteristic of SCWJ, the HTPB propellant erosion experiments were performed, and the relationship of the SCWJ unsteady characteristic and the erosion results on HTPB propellant was analyzed. The results show that the SCWJ develops in the flow field including inception, development, shedding, and collapse stages, the maximum density of cavitation cloud changes exponentially, and the cavitation cloud length grows as the cavitation numbers increase. Lower cavitation number is always beneficial to high penetration rate and low energy consumption when erosion on the HTPB propellant. When the erosion time of 120 s, in high cavitation number under the least amount of energy consumed, the unit energy consumption minimum. The mass loss curve is double peak, the first peak is caused by water jet effect, standoff distance is located on the stage of development, the formation of erosion pit diameter is small, the depth is larger, the second peak is caused by cavitation effect, and its standoff distance is located on the shedding phase, forming the erosion pit diameter is bigger, the depth is shallow. The optimum standoff distance for the cavitation effect for the cavitation numbers 0.0135, 0.0081, 0.0058 and 0.0045 is 35 mm, 50 mm, 60 mm and 70 mm in order, and the mass loss rate of HTPB propellant is 90 mg s−1, 200 mg s−1, 277 mg s−1 and 521 mg s−1, respectively. At best cavitation effect standoff distance, cavitation number by 2 times, mass loss rate can increase 3 times. The matrix brittle fractures occur when the SCWJ strikes the HTPB propellant at a high strain rate. Besides, the erosion mechanism of HTPB propellant is discussed.

Summary: Uveitis, an autoimmune disease, often leads to blindness. CD4+ T cells, including regulatory T cells (Tregs) and effector T cells (Th1 and Th17), play a critical role in its pathogenesis. Caloric restriction (CR) has been shown to alleviate autoimmune diseases. However, careful characterization of the impact of CR on experimental autoimmune uveitis (EAU) is poorly understood. This study used single-cell RNA sequencing to analyze cervical draining lymph nodes in mice under ad libitum (AL) and CR diets, with or without EAU. CR increased Tregs, altered immune cell metabolism, reduced EAU symptoms, and downregulated inflammatory and glycolysis genes. Flow cytometry confirmed CR’s inhibitory effect on Th1 and Th17 proliferation and its promotion of Treg proliferation. CR also balanced CD4+ T cells by inhibiting the PI3K/AKT/c-Myc pathway and reducing GM-CSF in Th17 cells. These findings suggest CR as a potential therapeutic strategy for autoimmune diseases.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

Sturgeons (Acipenseridae), ancient fish known for their caviar, produce underutilized by-products like protein-rich cartilage, which is a source of high-quality bioactive peptides. This study investigates immunomodulatory peptides from sturgeon cartilage hydrolysates mechanisms. The study found that sturgeon cartilage hydrolysate F2–7 and its key peptides(DHVPLPLP and HVPLPLP)significantly promoted RAW267.4 cell proliferation, NO release, and phagocytosis (P

Abstract Atomically dispersed single‐atom catalysts (SACs) on carbon supports show great promise for H2O2 electrosynthesis, but conventional wet chemistry methods using particulate carbon blacks in powder form have limited their potential as two‐electron (2e−) oxygen reduction reaction (ORR) catalysts. Here, we demonstrate high‐performance Co SACs supported on a free‐standing aligned carbon nanofiber (CNF) using electrospinning and arc plasma deposition (APD). Based on the surface oxidation treatment of aligned CNF and precise control of the deposition amount in a dry‐based APD process, we successfully form densely populated Co SACs on aligned CNF. Through experimental analyses and density functional theory calculations, we reveal that Co SAC has a Co–N2–O2 moiety with one epoxy group, leading to excellent 2e− ORR activity. Furthermore, the aligned CNF significantly improves mass transfer in flow cells compared to randomly oriented CNF, showing an overpotential reduction of 30 mV and a 1.3‐fold improvement (84.5%) in Faradaic efficiency, and finally achieves an outstanding production rate of 15.75 mol gcat−1 h−1 at 300 mA cm−2. The high‐performance Co SAC supported on well‐aligned CNF is also applied in an electro‐Fenton process, demonstrating rapid removal of methylene blue and bisphenol F due to its exceptional 2e− ORR activity.

BackgroundCerebral syphilitic gumma (CSG), a rare manifestation of neurosyphilis, presents characteristics akin to intracranial tumors, often leading to clinical misdiagnosis.ObjectiveThis study aimed to summarize the clinical experience in diagnosing and treating CSG.Materials and methodsThe present study conducted a retrospective analysis of clinical data, encompassing the baseline characteristics, clinical presentation, diagnosis, treatment, and prognosis of eight patients with CSG who were treated and diagnosed by our institution.ResultsThe median age at the initial diagnosis was 57.5 years, comprising six males and two females. The predominant clinical manifestations included headaches in eight cases, motor and sensory disorders in four cases, epileptic seizures in one case, and dysarthria in one patient. The serum Treponema pallidum haemagglutination assay (TPHA) and toluidine red unheated serum test (TRUST) yielded positive in all eight patients. The contrast-enhanced magnetic resonance imaging (MRI) revealed irregular ring-shaped enhancement of lesions in three patients, while nodular enhancement of lesions was observed in five patients. In terms of treatment, seven patients underwent surgery. The postoperative pathological tissue showed granulomatous inflammation. Six patients exhibited an elevated protein concentration in their cerebrospinal fluid (CSF), while two patients demonstrated a reduced CSF glucose level. Additionally, positive results were obtained for both CSF TPHA and TRUST in all eight patients. The clinical diagnosis of CSG was confirmed in eight patients who exhibited notable clinical improvement following penicillin treatment. Subsequent reevaluation of the imaging findings demonstrated complete resolution of the enhanced lesions.ConclusionIn clinical practice, CSG should be considered for patients with intracranial lesions and positive serum syphilis antibodies. Timely and accurate diagnosis enables patients with CSG to achieve a more favorable prognosis through active anti-syphilis treatment.

Abstract The precise and effective activation of the immune response is crucial in promising therapy curing cancer. Photoimmunotherapy (PIT) is an emerging strategy for precise regulation and highly spatiotemporal selectivity. However, this approach faces a significant challenge due to the off‐target effect and the immunosuppressive microenvironment. To address this challenge, a nanoscale full‐active pharmaceutical ingredient (API) photo‐immune stimulator was developed. This formulation overcomes the limitations of PIT by strengthening the ability to penetrate tumors deeply and inducing precise and potent mitochondria‐targeted dual‐mode photodynamic therapy and photothermal therapy. Along with inhibiting overexpressed Hsp90, this nanosensitizer in turn improves the immunosuppressive microenvironment. Ultimately, this mitochondria‐targeted PIT demonstrated potent antitumor efficacy, achieving a remarkable inhibition rate of ≥95% for both established primary tumors and distant abscopal tumors. In conclusion, this novel self‐delivery full‐API nanosystem enhances the efficacy of phototherapy and reprograms the immunosuppressive microenvironment, thereby holding great promise in the development of precise and effective immunotherapy.

Abstract Lesion segmentation is a fundamental task in medical image processing, often facing the challenge of subtle lesions. It is important to detect these lesions, even though they can be difficult to identify. Convolutional neural networks, an effective method in medical image processing, often ignore the relationship between lesions, leading to topological errors during training. To tackle topological errors, move is made from pixel‐level to hypergraph representations. Hypergraphs can model lesions as vertices connected by hyperedges, capturing the topology between lesions. This paper introduces a novel dynamic hypergraph learning strategy called DHLS. DHLS allows for the dynamic construction of hypergraphs contingent upon input vertex variations. A hypergraph global‐aware segmentation network, termed HGSNet, is further proposed. HGSNet can capture the key high‐order structure information, which is able to enhance global topology expression. Additionally, a composite loss function is introduced. The function emphasizes the global aspect and the boundary of segmentation regions. The experimental setup compared HGSNet with other advanced models on medical image datasets from various organs. The results demonstrate that HGSNet outperforms other models and achieves state‐of‐the‐art performance on three public datasets.

Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted. Results The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer. Conclusion [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis. Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

In this article, a standalone executable software molVisual3D, for 3D visualization of molecules was developed. It uses the XYZ file of a molecule to generate its 3D graphics. Some parameters can be specified by the user. In the generated 3D graphics window, the user can right- or left-click mouse to zoom in or zoom out the 3D graphics, or mouse-drag the graphics to rotate the 3D graphics, or slide scrollbar to vertically or horizontally translate the 3D graphics. The 3D graphics can be saved into an image file (in BMP format). Both molVisual3D and demonstration data files were given.

Dependent upon the statistical significance p-value and statistical power, the sample size estimation is widely used in various experimental sciences. Nevertheless, the p-value based paradigm, which has resulted in numerous fake conclusions that originate partly from insufficient sample sizes, has been widely criticized in recent years for serious problems. Therefore, I developed a platform-independent computational tool, SampSizeCal, for sample sizes in the paradigm of new statistics. In this tool, both default p-values and the maximum p-values were greatly enhanced, which will lead to the reasonable increase of sample sizes. The computational tool harbors more than 120 sample size methods for experimental designs. SampSizeCal includes both online and offline versions, and can be used for various computing devices (PCs, iPads, smartphones, etc.), operating systems (Windows, Mac, Android, Harmony, etc.) and web browsers (Chrome, Firefox, Sougo, 360, etc). It is currently the most comprehensive platform-independent computational tool for sample sizes, and can be used in experimental sciences such as medicine (clinical medicine, experimental zoology, public health, pharmacy, etc.), biology, ecology, agronomy, psychology and engineering technology.

Meta-analysis is a statistical method used in systematic review to quantitatively integrate the results of multiple related studies to obtain a pooled result that can represent these studies. Meta-analysis overcomes the limitations of traditional reviews that only conduct qualitative research. In present study, I developed a platform-independent computational tool for meta-analysis. It is a comprehensive tool consisting of a full set of meta-analysis methodology, including the methods for fixed-effects model and random-effects model and the methods for heterogenetity testing in which the effect size tests based heterogeneity testing were proposed. Effect size tests of difference significance for post meta-analysis were also presented. The computational tool is a web browser based meta-analyzer that includes both online and offline versions and can be used on various computing devices (PCs, iPads, smartphones, etc.), operating systems (Windows, Mac, Android, Harmony, etc.) and web browsers (Chrome, Firefox, etc). It can be used in various sciences as medicine, biology, ecology, psychology, sociology, economy, physics and chemistry etc.

The comparison of structural difference between biological communities and the evenness or diversity test of biological communities are always the focus in community studies. In present study, two computational tools were developed to conduct non-parametric statistical tests of between-community structural difference, among which a tool is for multi-samples comparison and the other is for single-sample comparison. Various distance measures are available for user’s choice. Two computational tools were developed to test community evenness and one tool was based on the randomization test proposed in present study and the other was based on Ewens-Caswell neutrality model. The computational tools include both online and offline versions and can be used on various computing devices (PCs, iPads, smartphones, etc.), operating systems (Windows, Mac, Android, Harmony, etc.) and web browsers (Chrome, Firefox, etc). They can be used in the sciences as ecology and biology, etc.

Abstract Wolfiporia cocos is a medicinal mushroom used in China. It biosynthesizes pachymic acid (PA), a main therapeutic triterpene associated with therapies. Nowadays, the unknown PA biosynthesis leads to difficulties in increasing its content in W. cocos. Herein, we report sequencing, assembling, and characterization of the genome and several transcriptomes of W. cocos. Sequence mining determined candidate genes that encode lanosterol synthase, sterol O-acyltransferase, and sterol C-24 methyltransferase likely involved in the steps from lanosterol to PA. Gene cluster analysis identified four CYP450 cDNAs likely involved in the biosynthesis of PA, namely WcCYP64-1, WcCYP64-2, WcCYP52, and WcCYP_FUM15, which were subjected to both overexpression and silencing in mycelia. The overexpression of each of WcCYP64-1, WcCYP52 and WcCYP_FUM15 increased the content of PA, 16α-hydroxytrametenolic acid, eburicoic acid, and tumulosic acid, while the silencing of each gene either significantly or slightly decreased the contents of these four compounds, indicating their involvement in the PA biosynthesis. In addition, different temperatures affected the expression of these genes and the formation of PA. By contrast, the overexpression and silencing of WcCYP64-2 did not alter the formation of these compounds. Taken together, these findings determine more potential steps in the biosynthetic pathway of PA for metabolic engineering.

Highlights High-quality large-area perovskite films are prepared using a solid–liquid two-step film formation method combined with CsBr modification for the buried interface and Urea additive for perovskite crystallization. The inverted perovskite solar modules’ performance is enhanced to 20.56% in 61.56 cm2 with improved stability.

Periodontal disease stands the leading cause of tooth loss in adults. While scaling and root planning is considered the “gold standard” treatment, it is often insufficient in efficiently eliminating anaerobic bacteria from deep periodontal pockets. In this work, an antibiotic-free and photo-curing hyaluronic acid-Janus (H-Janus) antibacterial pack was developed to inhibit the growth and colonization of residual bacteria within the pockets for reducing the recurrence of periodontitis. Our results demonstrated that a 4 wt% precursor solution of the antibacterial packs could be molded into various shapes by exposure to UV irradiation for less than 1 min, allowing the packs to seamlessly fill the irregular spaces of periodontal pockets. In vitro studies showed that the antibacterial packs gradually released lauric acid and oxygen over 7 days, exhibiting significant anti-biofilm effects against both aerobic and anaerobic bacteria. Notably, animal experiments confirmed that H-Janus antibacterial packs markedly improved the clinical scores in rats with periodontitis by inhibiting bacterial growth, alleviating inflammation, and fostering the regeneration of periodontal tissues. In light of their precise elimination of bacterial colonization and modulation of the infectious microenvironment, the H-Janus antibacterial packs show promising therapeutic potential for preventing the recurrence of periodontal pathogens following scaling and root planning.