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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.

To comprehensively evaluate the effects of drying methods on the nutritional quality and antioxidant activity of Jiangyong fragrant ginger, seven different drying methods including natural drying (ND), hot air drying (HAD), infrared drying (ID), microwave drying (MD), vacuum drying (VD), hot air-microwave combined drying (HAMCD), infrared-hot air combined drying (IHACD) were used to dry Jiangyong fragrant ginger. Thirteen indexes such as total phenols, total flavonoids, gingerols, curcumin, vitamin C, starch, cellulose, free amino acids, soluble protein, soluble sugar, DPPH free radical scavenging rate, hydroxyl radical scavenging rate and total reducing capacity of the dried samples were determined, and the core indexes were screened by principal component analysis. The comprehensive evaluation model of the quality of dried ginger was constructed for comprehensive scoring. The results showed that MD had the shortest drying time and the highest drying efficiency; The determination of quality indicators found that the total phenol content of ID was the highest; The total flavonoid content of ND was the highest; The gingerol, curcumin content and vitamin C content of MD were the highest; The starch content of HAD was the highest; The soluble sugar content of HAMCD was the highest; The soluble protein and free amino acid content of IHACD was the highest; The highest cellulose content and the best antioxidant activity were VD. Through principal component analysis, 13 quality indicators were summarized into four principal component factors, with contribution rates of 34.942%, 26.725%, 17.602%, and 12.016%, respectively, and the cumulative contribution rate was 91.285%. The quality evaluation model of Jiangyong fragrant ginger was established through principal component analysis, it was concluded that VD had the highest comprehensive score. The research results can provide a reference for the deep processing of Jiangyong fragrant ginger and the development of high-value products.

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.

This study was to evaluate the effect of fermented Gardenia jasminoides Ellis by a mixture of Bacillus sp. DU-106 and Lactobacillus plantarum on alcoholic oxidative damage in HepG2 cells. The CCK-8 method was used to explore the optimal alcoholic oxidative damage modelling concentration and the intervention concentration of Gardenia jasminoides Ellis extract. The effect of fermented Gardenia jasminoides Ellis extract on antioxidant capacity indicators such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA), glutathione (GSH) content, as well as the release of transaminase-like enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and indicators of evaluation of hepatic injury, such as pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), were detected. The results showed that Gardenia jasminoides Ellis extract (GE) and fermented Gardenia jasminoides Ellis extract (FGE) significantly increased the viability of ethanol-induced HepG2 cells (P

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.

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 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

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.

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.

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.

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 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 .

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.

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

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.

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.

Extracting the precise parameters of photovoltaic (PV) cells has become very important for simulation, evaluation, control, and optimization of PV systems. However, it is still a challenging task to accurately and reliably extract the parameters of PV cells. To solve this difficult problem, in this paper, a new meta-heuristic algorithm called Gaussian bare-bone imperialist competitive algorithm with opposition-based learning (OBL-GBBICA) is proposed to extract the parameters of PV cells. To strengthen the exploring ability and speed up the convergence, opposition-based learning (OBL) is introduced into an imperialist competitive algorithm (ICA) for two considerations. First, OBL is adopted in the population initialization to produce a high-quality population. Second, the OBL is introduced into the assimilation step to guide ICA to explore more promising regions. The above improvements not only speed up the convergence of ICA but also enhance its searchability, which is beneficial to improving the accuracy and reliability of identification results. Experimental results show that OBL-GBBICA exhibits great superiority in extracting the PV cells parameters, compared with other methods in the literature.

To improve the efficiency of photovoltaic systems, it is essential to obtain the parameters of photovoltaic cells through an identification process. However, due to the nonlinear and multimodal characteristics, accurately and reliably identifying the parameters of photovoltaic cells still remains a challenging task. In this paper, a hybrid of the imperialist competitive algorithm (ICA) and particle swarm optimization (PSO), ICA-PSO, is proposed to effectively identify the parameters of photovoltaic cells. The position updating strategy of PSO is adopted to replace the colony’s position updating strategy in the ICA. The hybrid algorithm ICA-PSO integrates the multi-swarm search characteristic and the powerful exploration ability of PSO together, leading to an enhanced optimization performance. Experimental results of applying ICA-PSO to parameter identification of photovoltaic cells show that ICA-PSO can extract the parameters of photovoltaic cells with higher accuracy and reliability, thus outperforming many other methods presented in the literature.

Abstract Metabolism‐related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies.

The phosphorus fate is critical to aquatic environment and ecosystem in lake. The relationship of phosphorus distribution in different mediums remains unknown under the fluctuation of phosphorus balance steady-state in lake. This study investigates the phosphorus balance of import and export in the Poyang Lake from 1990 to 2019, uncovering the transitional process of phosphorus balance steady-state and its influence on the phosphorus distribution relationship in different mediums. Our finding demonstrates that the phosphorus balance steady-state underwent four transitions during the study period of 1990–2019, resulting in a more fragile lake environment and ecosystem, with shorter intervals between quasi-balance states in Poyang Lake. The rate of sediment phosphorus burial and net phosphorus deposition increased significantly before the third phosphorus balance steady-state (2011–2013). However, the net deposition rate decreased by 5.3% with an increase in aquatic phosphorus after the third transition of phosphorus balance steady-state (2014) in Poyang Lake. Sediment played a significant role in redirecting from a net phosphorus sink to a net phosphorus source for water environment. The influence of phosphorus retention and sediment burial shifted from antagonism to synergism in increasing phosphorus content of waterbody, leading to a 5.4% rise in potential sources of aquatic phosphorus loading. These findings strengthen our understanding of phosphorus cycling and offer guidance for managing water environments in lakes. This work plays a vital role in regional water quality maintenance and water supply safety.

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.

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.

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.

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.

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.

Conventional orogenic settings are largely confined to plate boundaries and their immediate vicinity. However, there is growing recognition that deformation of the continental lithosphere may extend for considerable distances away from active plate boundaries. The Mesozoic Qilian orogenic belt occupies a key position in East Asia and thus is important to consider when interpreting intracontinental deformation there. To determine when and how the North Qilian orogenic belt developed, multiple sets of samples collected from the Dahuang Mountain of the North Qilian orogenic belt were analyzed for apatite (U-Th)/He and zircon (U-Th)/He thermochronology. The results show that the study area experienced multiphase tectonic exhumation events that took place in the Early-Middle Triassic (250–235 Ma), Middle-Late Jurassic (170–150 Ma), and Early Cretaceous (130–110 Ma). This study reveals that the generation deformation and stress distribution in the Dahuang Mountain fold-fault system have the characteristics of temporal–spatial migration from N to S. Results indicate widespread, continuous exhumation and deposition in the Qilian Mountain due to multiplate interaction since the Mesozoic, persisting till at least late Miocene. Multiphase intracontinental deformation is driven by stresses at plate boundaries, with lithosphere serving as stress pathway.