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With the development of science over the years, people have increasingly realized the importance of science communication. Unfortunately, very little research has focused on helping medical students develop the capabilities of science communication. To improve medical students' science communication and evaluate the effectiveness of New Media through mobile clients in health science communication, a competition was held among medical undergraduates. Outstanding works were selected for publication on our official health science communication WeChat account. Furthermore, the participants volunteered to complete a questionnaire survey to help us assess students' awareness of science communication. Our analysis revealed that students had a strong willingness to serve society and to participate in science communication work. Students generally agreed that science communication work had excellent effects on professional knowledge and related skills. In addition, the correlation results showed that the greater students' willingness to participate in health science communication was, the greater their sense of gain. New Media effectively expand the influence of students' popular science works. Our findings suggest that competition in science communication has a positive impact on enhancing students' awareness and capabilities in science communication. In addition, New Media are an effective way to improve students' scientific communication efficiency. However, we also noted that students' participation rate and enthusiasm for scientific communication were not high. Further research is needed to determine the reasons for this situation and potential strategies to further improve students' science communication.

Abstract Background UV-B, an important environmental factor, has been shown to affect the yield and quality of rice (Oryza sativa) worldwide. However, the molecular mechanisms underlying the response to UV-B stress remain elusive in rice. Results We perform comprehensive metabolic profiling of leaves from 160 diverse rice accessions under UV-B and normal light conditions using a widely targeted metabolomics approach. Our results reveal substantial differences in metabolite accumulation between the two major rice subspecies indica and japonica, especially after UV-B treatment, implying the possible role and mechanism of metabolome changes in subspecies differentiation and the stress response. We next conduct a transcriptome analysis from four representative rice varieties under UV-B stress, revealing genes from amino acid and flavonoid pathways involved in the UV-B response. We further perform a metabolite-based genome-wide association study (mGWAS), which reveals 3307 distinct loci under UV-B stress. Identification and functional validation of candidate genes show that OsMYB44 regulates tryptamine accumulation to mediate UV-B tolerance, while OsUVR8 interacts with OsMYB110 to promote flavonoid accumulation and UV-B tolerance in a coordinated manner. Additionally, haplotype analysis suggests that natural variation of OsUVR8 groupA contributes to UV-B resistance in rice. Conclusions Our study reveals the complex biochemical and genetic foundations that govern the metabolite dynamics underlying the response, tolerance, and adaptive strategies of rice to UV-B stress. These findings provide new insights into the biochemical and genetic basis of the metabolome underlying the crop response, tolerance, and adaptation to UV-B stress.

In order to reveal the influence of carnosic acid on the quality characteristics of thermal processed rapeseed oil, the changes of color, acid value, peroxide value, tocopherol, viscosity, fatty acid composition and total polar compound were investigated during thermal processing (180 ℃, 0, 8, 16, 24, 32 h) by adding different concentrations of carnosic acid (0, 200, 400, 700 mg/kg) and 200 mg/kg tert-butylhydroquinone as antioxidants. The results indicated that the addition of 700 mg/kg carnosic acid showed a better performance in the thermal processed rapeseed oil: The color deterioration was delayed and the increase of viscosity was inhibited; the increased value of acid value was the smallest which was from 0.280±0.030 mg/g to 0.757±0.020 mg/g, as well as the minimum peroxide value (0.138 g/100 g) was obtained at 32 h; the loss rate of α-tocopherol and γ-tocopherol were 95.51%±0.96% and 83.37%±0.39%, respectively; the content of polar components was 26.62%±0.03%, prolonging the thermal processing life of rapeseed oil by delaying the increase of total polar compound. It was found that the use of carnosic acid could better control the risk factors in rapeseed oil during thermal processing and reduce the waste of oils.

Abstract Objectives To explore the impact of hallux valgus (HV) on lower limb neuromuscular control strategies during the sit-to-stand (STS) movement, and to evaluate the effects of Kinesio taping (KT) intervention on these control strategies in HV patients. Methods We included 14 young healthy controls (HY), 13 patients in the HV group (HV), and 11 patients in the HV group (HVI) who underwent a Kinesio taping (KT) intervention during sit-to-stand (STS) motions. We extracted muscle and kinematic synergies from EMG and motion capture data using non-negative matrix factorization (NNMF). In addition, we calculated the center of pressure (COP) and ground reaction forces (GRF) to assess balance performance. Results There were no significant differences in the numbers of muscle and kinematic synergies between groups. In the HV group, knee flexors and ankle plantar flexors were abnormally activated, and muscle synergy D was differentiated. Muscle synergy D was not differentiated in the HVI group. Conclusion Abnormal activation of knee flexors and plantar flexors led to the differentiation of module D in HV patients, which can be used as an indicator of the progress of HV rehabilitation. KT intervention improved motor control mechanisms in HV patients.

Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Abstract Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC. Graphical Abstract

Defect engineering is an effective strategy for modifying the energy storage materials to improve their electrochemical performance. However, the impact of oxygen defect and its content on the electrochemical performances in the burgeoning aqueous NH4+ storage field remains explored. Therefore, for the first time in this work, an oxygen-defective ammonium vanadate [(NH4)2V10O25·8H2O, denoted as Od-NHVO] with a novel 3D porous flower-like architecture was achieved via the reduction of thiourea in a mild reaction condition, which is a facile method that can realize the intention to regulate the oxygen defect content, with the capability of mass-production. The as-prepared OdM-NHVO with moderate oxygen defect content can deliver a stable specific capacitance output (505 F g−1, 252 mAh g−1 at 0.5 A g−1 with ∼80% capacitance retention after 10,000 cycles), which benefits from extra active sites, unimpeded NH4+-migration path and relatively high structure integrity. In contrast, low oxygen defect content will lead to the torpid electrochemical reaction kinetics while too high content of it will reduce the charge-storage capability and induce structural disintegration. The superior NH4+-storage behavior is achieved with the reversible intercalation/de-intercalation process of NH4+ accompanied by forming/breaking of hydrogen bond. As expected, the assembled flexible OdM-NHVO//PTCDI quasi-solid-state hybrid supercapacitor (FQSS HSC) also exhibits high areal capacitance, energy density and reliable flexibility. This work provides a new avenue for developing materials with oxygen-deficient structure for application in various aqueous non-metal cation storage systems.

Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.

Abstract The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.

Abstract As promising energy-storage devices, zinc–air batteries (ZABs) exhibit slow reaction kinetics for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) occurring at their electrodes. High-performance bifunctional catalysts must thus be synthesized to accelerate the reversible conversion of oxygen and improve the rate and overall performance of ZABs. Herein, we reported the promising prospects of self-supported composite electrodes composed of wood-derived carbon (WDC) and bimetallic cobalt-iron alloys/oxides (CoFe-CoFe2O4@WDC) as efficient electrocatalysts for alkaline ORR/OER. WDC provided a favorable three-phase interface for heterogeneous reactions owing to its layered porous structure and genetic stability, thereby enabling mass diffusion and improving reaction kinetics. The CoFe2O4 spinel surface was reduced to bimetallic CoFe alloy to form abundant heterostructure interfaces that promote electron transfer. Under alkaline conditions, the optimized composite electrode exhibited a remarkable high half-wave potential of 0.85 V and an exceptionally low overpotential of 1.49 V. It also exhibited stable performance over an impressive 2340 cycles in a ZAB. Theoretical calculations also confirmed that the heterointerface addresses the issue of proton scarcity throughout the reaction and actively facilitates the creation of O–O bonds during the reversible transformation of oxygen. This study introduces a new concept for developing bifunctional and efficient electrocatalysts based on charcoal and encourages the sustainable and high-value use of forest biomass resources. Graphical Abstract

Abstract Single-frame infrared small target detection is affected by the low image resolution and small target size, and is prone to the problems of small target feature loss and positional offset during continuous downsampling; at the same time, the sparse features of the small targets do not correlate well with the global-local linkage of the background features. To solve the above problems, this paper proposes an efficient infrared small target detection method. First, this paper incorporates BlurPool in the feature extraction part, which reduces the loss and positional offset of small target features in the process of convolution and pooling. Second, this paper designs an interactive attention deep feature fusion module, which acquires the correlation information between the target and the background from a global perspective, and designs a compression mechanism based on deep a priori knowledge, which reduces the computational difficulty of the self-attention mechanism. Then, this paper designs the context local feature enhancement and fusion module, which uses deep semantic features to dynamically guide shallow local features to realize enhancement and fusion. Finally, this paper proposes an edge feature extraction module for shallow features, which utilizes the complete texture and location information in the shallow features to assist the network to initially locate the target position and edge shape. Numerous experiments show that the method in this paper significantly improves nIoU, F1-Measure and AUC on IRSTD-1k Datasets and NUAA-SIRST Datasets.

Abstract This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

Abstract Background The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.

Abstract Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding modes of such drifted hemagglutinin’s (HAs) are examined by chemoenzymatic synthesis of N-glycans having 13C-labeled monosaccharides at strategic positions. The labeled glycans are employed in 2D STD-1H by 13C-HSQC NMR experiments to pinpoint which monosaccharides of the extended LacNAc chain engage with evolutionarily distinct HAs. The NMR data in combination with computation and mutagenesis demonstrate that mutations distal to the receptor binding domain of recent HAs create an extended binding site that accommodates with the extended LacNAc chain. A fluorine containing sialoside is used as NMR probe to derive relative binding affinities and confirms the contribution of the extended LacNAc chain for binding.

IntroductionThe massive loss of global glacier mass caused by climate problems has caused concern, while the Earth’s rotation as the most significant form of motion has also been subtly affected. However, the quantitative effects of massive glaciers losing mass on Earth’s rotation have not been revealed.MethodsHerein, the knowledge of moment of inertia and suitable rotational inertia models in classical mechanics is initially utilized to assess the effect of quantitative glaciers losing mass on Earth's rotation.ResultsAfter specific calculations, the putative 200 billion tons of glaciers losing mass bring on an increase of 1.4099×10-4s in Earth’s rotation time in 365 days.DiscussionThis work examines the connection between glaciers losing mass and Earth’s rotation from classical mechanics, thus providing the way for investigations of relationship between climate changes and Earth.

Abstract A challenging task in solid oxide fuel cells (SOFCs) is seeking for an alternative electrolyte, enabling high ionic conduction at relatively low operating temperatures, i.e., 300–600 °C. Proton‐conducting candidates, in particular, hold a significant promise due to their low transport activation energy to deliver protons. Here, a unique hierarchical TiO2‐SrTiO3@TiO2 structure is developed inside an intercalated TiO2‐SrTiO3 core as “yolk” decorating densely packed flake TiO2 as shell, creating plentiful nano‐heterointerfaces with a continuous TiO2 and SrTiO3 “in‐house” interfaces, as well the interfaces between TiO2‐SrTiO3 yolk and TiO2 shell. It exhibits a reduced activation energy, down to 0.225 eV, and an unexpectedly high proton conductivity at low temperature, e.g., 0.084 S cm−1 at 550 °C, confirmed by experimentally H/D isotope method and proton‐filtrating membrane measurement. Raman mapping technique identifies the presence of hydrogenated HO─Sr bonds, providing further evidence for proton conduction. And its interfacial conduction is comparatively analyzed with a directly‐mixing TiO2‐SrTiO3 composite electrolyte. Consequently, a single fuel cell based on the TiO2‐SrTiO3@TiO2 heterogeneous electrolyte delivers a good peak power density of 799.7 mW cm−2 at 550 °C. These findings highlight a dexterous nano‐heterointerface design strategy of highly proton‐conductive electrolytes at reduced operating temperatures for SOFC technology.

Abstract Background Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level. Methods We performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses. Results LSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Conclusions Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

Background and objectivesThe advent of new clinical subtyping systems for Parkinson's disease (PD) has led to the classification of patients into distinct groups: mild motor predominant (PD-MMP), intermediate (PD-IM), and diffuse malignant (PD-DM). Our goal was to evaluate the efficacy of diffusion tensor imaging (DTI) in the early diagnosis, assessment of clinical progression, and prediction of prognosis of these PD subtypes. Additionally, we attempted to understand the pathological mechanisms behind white matter damage using single-photon emission computed tomography (SPECT) and cerebrospinal fluid (CSF) analyses.MethodsWe classified 135 de novo PD patients based on new clinical criteria and followed them up after 1 year, along with 45 healthy controls (HCs). We utilized tract-based spatial statistics to assess the microstructural changes of white matter at baseline and employed multiple linear regression to examine the associations between DTI metrics and clinical data at baseline and after follow-up.ResultsCompared to HCs, patients with the PD-DM subtype demonstrated reduced fractional anisotropy (FA), increased axial diffusivity (AD), and elevated radial diffusivity (RD) at baseline. The FA and RD values correlated with the severity of motor symptoms, with RD also linked to cognitive performance. Changes in FA over time were found to be in sync with changes in motor scores and global composite outcome measures. Furthermore, baseline AD values and their rate of change were related to alterations in semantic verbal fluency. We also discovered the relationship between FA values and the levels of α-synuclein and β-amyloid. Reduced dopamine transporter uptake in the left putamen correlated with RD values in superficial white matter, motor symptoms, and autonomic dysfunction at baseline as well as cognitive impairments after 1 year.ConclusionsThe PD-DM subtype is characterized by severe clinical symptoms and a faster progression when compared to the other subtypes. DTI, a well-established technique, facilitates the early identification of white matter damage, elucidates the pathophysiological mechanisms of disease progression, and predicts cognitively related outcomes. The results of SPECT and CSF analyses can be used to explain the specific pattern of white matter damage in patients with the PD-DM subtype.

The inhibition of return (IOR) is a phenomenon where response times (RTs) to a target appearing at a previously cued location are slower than those for an uncued location. IOR can improve visual search efficiency. This study aimed to investigate IOR in badminton athletes at different cue depths using a cue-target paradigm in three-dimensional (3-D) static and dynamic scenarios. The study involved 28 badminton athletes (M age = 21.29, SD = 2.39, 14 males) and 25 non-athletes (M age = 21.56, SD = 2.38, 11 males). In the static scenario (Experiment 1), no significant difference between IOR in cueing near and far conditions. IOR was showed both in cueing the near and far condition. Badminton athletes had a speed advantage than non-athletes. In the dynamic scenario (Experiment 2), only badminton athletes showed IOR in cueing the far-to-near condition, but not for the near-to-far. The present study showed that depth information influenced the IOR only in far-to-near condition. Badminton athletes showed more sensitivity to depth information than non-athletes. Additionally, the study expands the object-based IOR in 3-D dynamic scenario.

With the proposal of the 2030 Agenda for Sustainable Development, the Chinese medicine extraction technology has been innovatively improved to prioritize low energy consumption, sustainability, and minimized organic solvent utilization. Forsythia suspensa (FS) possesses favorable pharmacological properties and is extensively utilized in traditional Chinese medicine. However, due to the limitations of the composition and extraction methods, its potential has not been fully developed. Thus, a combination of ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), and β-cyclodextrin extraction (β-CDE) was employed to isolate and purify rutin, phillyrin, and forsythoside A from FS. The results demonstrated that the efficiency of extracting enzymatic and ultrasound assisted β-cyclodextrin extraction (EUA-β-CDE) was highly influenced by the temperature and duration of hydrolysis, as well as the duration of the extraction process. According to the results of the single-factor experiment, Box-Behnken design (BBD) in Response surface method (RSM) was used to optimize the experimental parameters to achieve the maximum comprehensive evaluation value (CEV) value. The EUA-β-CDE compared with other extraction methods, has good extraction effect and low energy consumption by high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), calculation of power consumption and CO2 emission The EUA-β-CDE compared with other extraction methods, has good extraction effect and low energy consumption by HPLC, SEM, calculation of power consumption and CO2 emission. Then, the structural characteristics of EUA-β-CDE of FS extract had significant interaction with β-CD by Fourier infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In addition, EUA-β-CDE extract has good antioxidant and anti-inflammatory activities. The establishment of EUA-β-CDE of FS provides a new idea for the development and application of other sustainable extraction methods of traditional Chinese medicine.

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

Abstract Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region. Furthermore, OTUD1-based aggresomes recruit ASK1 via protein-protein interactions, which in turn stabilize ASK1 in a deubiquitinase-independent manner and activate the downstream JNK signaling pathway for OCSC maintenance. Notably, the disruption of OTUD1-based aggresomes or treatment with ASK1/JNK inhibitors, including ibrutinib, an FDA-approved drug that was recently identified as an MKK7 inhibitor, effectively reduced OCSC stemness (OSCS) of OTUD1high ovarian cancer cells. In summary, our work suggests that aggresome formation in tumor cells could function as a signaling hub and that aggresome-based therapy has translational potential for patients with OTUD1high ovarian cancer.

To investigate the biomechanical mechanisms underlying the pathogenesis and explore the effects of kinesiology taping (KT) on neuromuscular control in HV patients. The study population consisted of 16 young controls (YC group) and 15 patients with hallux valgus (HV group). All subjects underwent a natural velocity gait assessment. Additionally, 11 patients from the HV group received KT intervention over a period of one month, consisting of 15 sessions administered every other day. After the one-month intervention, these patients underwent a gait assessment and were included in the HV-KT group. The electromyography (EMG) and joint motion were evaluated using non-negative matrix factorization (NNMF) to compare the difference in muscle and kinematic synergy among the three groups. The center of plantar pressure (COP) and ground reaction force (GRF) were measured by the force platform. The number of synergies did not differ within the three groups, but the structure of muscle synergies and kinematic synergies differed in the HV group. The KT intervention (HV-KT group) altered the structure of synergies. The correlation between kinematic synergies and muscular synergies was lower in the HV group than in the YC group, whereas the correlation between the two increased after the KT intervention in the HV group. During gait, the HV group tended to activate more muscles around foot joints to maintain body stability. The visual analogue scale (VAS) scores, hallux valgus angle (HVA), and COP were significantly decreased after the intervention ( ${P}\lt 0.05$ ). HV patients exhibited altered kinematic and muscular synergies structures as well as muscle activation. Also, it weakened the balance and athletic ability of HV patients. KT intervention improved neuromuscular control to provide a better gait performance.

Abstract Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e−) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.

In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People’s Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient’s sputum, confirming the H10N3 infection. The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health. Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count

Abstract The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new‐generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass‐derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass‐derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass‐derived CAC‐based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass‐derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass‐derived CAC‐based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass‐derived CAC electrocatalysis and electric energy storage.

BackgroundYoung women often face substantial psychological challenges in the initial years following cancer diagnosis, leading to a comparatively lower quality of life than older survivors. While mobile apps have emerged as potential interventions, their effectiveness remains inconclusive due to the diversity in intervention types and variation in follow-up periods. Furthermore, there is a particular dearth of evidence regarding the efficacy of these apps’ intelligent features in addressing psychological distress with these apps. ObjectiveThis study aims to evaluate the effectiveness of a mobile app with intelligent design called “AI-TA” on cancer-related psychological health and ongoing symptoms with a randomized controlled design. MethodsWomen aged 18 to 45 years diagnosed with breast cancer were randomly assigned to the intervention or control group. The intervention was AI-TA, which included 2-way web-based follow-up every 2 weeks. Both intention-to-treat (ITT) and per-protocol (PP) analyses employed repeated measurement analysis of variance. The participants’ background features, primary outcomes (psychological distress and frequency, self-efficacy, and social support), and secondary outcomes (quality of life) were measured using multiple instruments at 3 time points (baseline, 1-month intervention, and 3-month intervention). ResultsA total of 124 participants were randomly allocated to the control group (n=62, 50%) or intervention group (n=62, 50%). In total, 92.7% (115/124) of the participants completed the intervention. Significant improvements in psychological symptoms (Memorial Symptom Assessment Scale-Short Form) were observed in the ITT group from baseline to 1-month intervention relative to the control group (ITT vs control: 1.17 vs 1.23; P

ObjectiveThis study aimed to assess the impact of gestational diabetes mellitus (GDM) on fetal heart structure and function using a technique called fetal heart quantification (Fetal HQ), with a focus on mitochondrial dynamics, which employs advanced imaging technology for comprehensive analysis.MethodsA total of 180 fetuses with normal heart structures, aged 24–40 weeks of gestation, were examined. A 2–3 s cine loop in the standard four-chamber oblique view was captured and analyzed using the speckle-tracking technique with Fetal HQ. Various echocardiographic parameters were evaluated, including four-chamber view (4CV), global spherical index (GSI), global longitudinal strain (GLS), 24-segment spherical index (SI), ventricular fractional area change (FAC), cardiac output (CO), and stroke volume (SV). These parameters were compared between the GDM group and the control group during two gestational periods: 24+0 to 28+0 weeks and 28+1 to 40+1 weeks. Statistical analysis was performed using independent samples t-tests and Mann-Whitney U tests to identify significant differences.ResultsTwenty fetuses from mothers with GDM and 40 from the control group were recruited at 24+0 to 28+0 weeks. At 28+1 to 40+1 weeks, 40 fetuses from mothers with GDM and 80 from the control group were recruited. The fetal left ventricular global longitudinal function was similar between the GDM and control groups. However, compared to the controls, right ventricular function in the GDM group was lower only at 28+1 to 40+1 weeks. In the GDM group, the global spherical index (GSI) was lower than in the control group at 28+1 to 40+1 weeks (1.175 vs. 1.22; p = 0.001). There were significant decreases in ventricular FAC (38.74% vs. 42.83%; p < 0.0001) and 4CV GLS for the right ventricle (−22.27% vs. −26.31%; p = 0.005) at 28+1 to 40+1 weeks.ConclusionOur findings suggest that GDM is associated with decreased right ventricular function in the fetal heart, particularly during the later stages of pregnancy (28+1 to 40+1 weeks), compared to fetuses from healthy pregnancies. The Fetal HQ technique represents a valuable tool for evaluating the structure and function of fetal hearts affected by GDM during the advanced stages of pregnancy.

Abstract Background Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD‐L1 translocation in various tumor cells. Methods C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD‐L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD‐L1‐related pathways after being treated with PPIs. The related gene expression is performed by qRT‐PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD‐L1 in the tissue samples by immunohistochemistry. Results We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD‐L1 on cell membrane at clinically relevant concentrations. Furthermore, pre‐treatment with PPIs appeared to synergize the efficiency of anti‐PD‐L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD‐L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3β, then leading to PD‐L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD‐L1 was negated following GSK3β knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD‐L1 expression in esophageal cancer patients. Conclusion We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD‐L1 by inducing GSK3β phosphorylation and facilitate primary tumor progression and metastasis.

Spike architecture influences both grain weight and grain number per spike, which are the two major components of grain yield in bread wheat (Triticum aestivum L.). However, the complex wheat genome and the influence of various environmental factors pose challenges in mapping the causal genes that affect spike traits. Here, we systematically identified genes involved in spike trait formation by integrating information on genomic variation and gene regulatory networks controlling young spike development in wheat. We identified 170 loci that are responsible for variations in spike length, spikelet number per spike, and grain number per spike through genome-wide association study and meta-QTL analyses. We constructed gene regulatory networks for young inflorescences at the double ridge stage and the floret primordium stage, in which the spikelet meristem and the floret meristem are predominant, respectively, by integrating transcriptome, histone modification, chromatin accessibility, eQTL, and protein–protein interactome data. From these networks, we identified 169 hub genes located in 76 of the 170 QTL regions whose polymorphisms are significantly associated with variation in spike traits. The functions of TaZF-B1, VRT-B2, and TaSPL15-A/D in establishment of wheat spike architecture were verified. This study provides valuable molecular resources for understanding spike traits and demonstrates that combining genetic analysis and developmental regulatory networks is a robust approach for dissection of complex traits.

Summary: Hydrogen generation from boron hydride is important for the development of hydrogen economy. Cobalt (Co) element has been widely used in the hydrolysis of boron hydride. Pyrolysis is a common method for materials synthesis in catalytic fields. Herein, Co-based nanocomposites derived from the pyrolysis of organic metal precursors and used for hydrolysis of boron hydride are summarized and discussed. The different precursors consisting of MOF, supported, metal, and metal phosphide precursors are summarized. The catalytic mechanism consisting of dissociation mechanism based on oxidative addition-reduction elimination, pre-activation mechanism, SN2 mechanism, four-membered ring mechanism, and acid-base mechanism is intensively discussed. Finally, conclusions and outlooks are conveyed from the design of high-efficiency catalysts, the characterization of catalyst structure, the enhancement of catalytic activities, the investigation of the catalytic mechanism, and the catalytic stability of active structure. This review can provide guidance for designing high-efficiency catalysts and boosting development of hydrogen economy.

Summary: Zeolite-encaged metal nanoparticles (NPs) catalysts are emerging as a new frontier owing to their superior ability to stabilize the structure and catalytic performance in the thermal and environmental catalytic reaction. However, the pore size below 2 nm of the conventional zeolites usually limits the accessibility of metal active sites. Herein, Co-Cu NPs of about 2.5–3.5 nm were uniformly encapsulated in the intracrystalline mesoporous Silicalite-1 (S-1) through alkali-treatment ligand-assisted strategy. The obtained sample (termed CoxCu1-x@HS-1) exhibited efficient activity and stability in the ammonia borane hydrolysis with the highest TOF value of 21.46 molH2·molMe−1·min−1. UV–vis DRS spectra indicated that intracrystalline mesopores have greatly improved the openness and accessibility of the active sites, thus improving their catalytic performance. The introduction of Cu regulates the electronic properties of Co, further increasing hydrogen production activity. This research creates new prospects to design other high-performance hierarchical porous zeolite-confined metal/metal oxide catalysts.

Abstract Background To establish a long-term mechanism to control the cost burden of drugs, the Chinese government organized seven rounds of price negotiations for the national reimbursement drug list (NRDL) from 2016 to the end of 2022. The study aimed to evaluate the impact of the National Health Insurance Coverage (NHIC) policy on the use of lenvatinib as the first-line treatment for advanced hepatocellular carcinoma (HCC) within a specific medical insurance region from the micro perspective of individual patient characteristics. Methods The data of HCC patients that received lenvatinib from September 2019 to August 2022 was retrieved from the Medical and Health Big Data Center and longitudinally analyzed. Contingency table chi-square statistics and binary logistic regression analysis were used to compare the differences in the categorical variables. Interrupted time-series (ITS) regression analysis was performed to evaluate the changes in the utilization of lenvatinib over 36 months. Multiple linear regression was used to analyze the impact of receiving lenvatinib on the total hospitalization expenses of hospitalized patients with advanced HCC. Results A total of 12,659 patients with advanced HCC were included in this study. The usage rate of lenvatinib increased from 6.19% to 15.28% over 36 months (P

AbstractOsteoporosis is a common disease among the ageing society. Oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) is the aetiology of osteoporosis. α-Lipoic acid (ALA) is an antioxidant in the body, which can eliminate excess ROS in the body and inhibits levels of oxidative stress in cells. Herein, we designed PEGylated hollow gold nanoparticles (HGNPs) loaded with ALA (mPEG@HGNPs-ALA) to remove ROS in the treatment of osteoporosis. First, mPEG@HGNPs with a particle size of ∼63 nm has been successfully synthesized. By comparing the drug loading of mPEG@HGNPs, it was concluded that the optimal mass ratio of mPEG@HGNPs (calculated by the amount of gold) to ALA was ∼1:2. ABTS antioxidant assay showed that free radical removal ability. In vitro results revealed that the preparation had good biocompatibility. At the gold concentration of 1–150 μg/mL, the cell viability of mPEG@HGNPs was more than 100%, which indicated that it could promote the proliferation of osteoblasts. What’s more, mPEG@HGNPs-ALA could effectively remove the ROS caused by H2O2 injury and improve the cell viability. According to these results, it can be considered that mPEG@HGNPs-ALA has the potential to treat osteoporosis.

Abstract Background Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. Methods We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. Results In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. Conclusion For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms that consist of social deficits and repetitive behaviors. Unfortunately, no effective medication is available thus far to target the core symptoms of ASD, since the pathogenesis remains largely unknown. To investigate the pathogenesis of the core symptoms in ASD, we constructed Shank1 P1812L-knock-in (KI) mice corresponding to a recurrent ASD-related mutation, SHANK1 P1806L, to achieve construct validity and face validity. Shank1 P1812L-KI heterozygous (HET) mice presented with social deficits and repetitive behaviors without the presence of confounding comorbidities. HET mice also exhibited downregulation of metabotropic glutamate receptor (mGluR1) and associated signals, along with structural abnormalities in the dendritic spines and postsynaptic densities. Combined with findings from Shank1 R882H-KI mice, our study confirms that mGluR1-mediated signaling dysfunction is a pivotal mechanism underlying the core symptoms of ASD. Interestingly, Shank1 P1812L-KI homozygous (HOM) mice manifested behavioral signs of impaired long-term memory rather than autistic-like core traits; thus, their phenotype was markedly different from that of Shank1 P1812L-KI HET mice. Correspondingly, at the molecular level, Shank1 P1812L-KI HOM displayed upregulation of AMPA receptor (GluA2)-related signals. The different patterns of protein changes in HOM and HET mice may explain the differences in behaviors. Our study emphasizes the universality of mGluR1-signaling hypofunction in the pathogenesis of the core symptoms in ASD, providing a potential target for therapeutic drugs. The precise correspondence between genotype and phenotype, as shown in HOM and HET mice, indicates the importance of reproducing disease-related genotypes in mouse models.

Abstract Endonuclease G (ENDOG), a nuclear-encoded mitochondrial intermembrane space protein, is well known to be translocated into the nucleus during apoptosis. Recent studies have shown that ENDOG might enter the mitochondrial matrix to regulate mitochondrial genome cleavage and replication. However, little is known about the role of ENDOG in the cytosol. Our previous work showed that cytoplasmic ENDOG competitively binds with 14-3-3γ, which released TSC2 to repress mTORC1 signaling and induce autophagy. Here, we demonstrate that cytoplasmic ENDOG could also release Rictor from 14-3-3γ to activate the mTORC2-AKT-ACLY axis, resulting in acetyl-CoA production. Importantly, we observe that ENDOG could translocate to the ER, bind with Bip, and release IRE1a/PERK to activate the endoplasmic reticulum stress response, promoting lipid synthesis. Taken together, we demonstrate that loss of ENDOG suppresses acetyl-CoA production and lipid synthesis, along with reducing endoplasmic reticulum stress, which eventually alleviates high-fat diet-induced nonalcoholic fatty liver disease in female mice.

Lactobacillus acidophilus is a probiotic bacterium that possesses numerous health-promoting properties and has significant technological applications in the fermentation of a wide range of food products and beverages. This review discusses the health benefits of L. acidophilus, including its ability to enhance immunity; promote digestive wellness; and exhibit antioxidant, antitumor, and antimicrobial properties. This review also discusses the production of bioactive peptides and extracellular polysaccharides (EPS) by L. acidophilus. Factors, such as salinity, temperature, carbon sources, and nutrient availability, influence the growth of L. acidophilus, which can affect the survival and bioactive potential of fermented products. The proteolytic effects of L. acidophilus contribute to protein breakdown, which leads to the release of bioactive peptides with various health benefits. This review also discusses the applications of L. acidophilus in the fermentation of dairy products, cereal beverages, soymilk, fruit and vegetable juices, and other functional food preparations, highlighting its potential for improving the nutritional value, organoleptic properties, and probiotic delivery of these products. This review highlights the importance of understanding and controlling fermentation conditions to maximize the growth and health-promoting benefits of L. acidophilus in various food and beverage products.

Cancer is a leading cause of death worldwide, and the development of new diagnostic and treatment methods is crucial. Manganese-based nanomaterials (MnNMs) have emerged as a focal point in the field of cancer diagnosis and treatment due to their multifunctional properties. These nanomaterials have been extensively explored as contrast agents for various imaging technologies such as magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and near-infrared fluorescence imaging (NIR-FL). The use of these nanomaterials has significantly enhanced the contrast for precise tumor detection and localization. Moreover, MnNMs have shown responsiveness to the tumor microenvironment (TME), enabling innovative approaches to cancer treatment. This review provides an overview of the latest developments of MnNMs and their potential applications in tumor diagnosis and therapy. Finally, potential challenges and prospects of MnNMs in clinical applications are discussed. We believe that this review would serve as a valuable resource for guiding further research on the application of manganese nanomaterials in cancer diagnosis and treatment, addressing the current limitations, and proposing future research directions.

Summary: Titanium silicate zeolite (TS-1) is widely used in the research on selective oxidations of organic substrates by H2O2. Compared with the chlorohydrin process and the hydroperoxidation process, the TS-1 catalyzed hydroperoxide epoxidation of propylene oxide (HPPO) has advantages in terms of by-products and environmental friendliness. This article reviews the latest progress in propylene epoxidation catalyzed by TS-1, including the HPPO process and gas phase epoxidation. The preparation and modification of TS-1 for green and sustainable production are summarized, including the use of low-cost feedstocks, the development of synthetic routes, strategies to enhance mass transfer in TS-1 crystal and the enhancement of catalytic performance after modification. In particular, this article summarizes the catalytic mechanisms and advanced characterization techniques for propylene epoxidation in recent years. Finally, the present situation, development prospect and challenge of propylene epoxidation catalyzed by TS-1 were prospected.

Abstract Chronic pain is a major cause of suffering that often accompanies diseases and therapies, affecting approximately 20% of individuals at some point in their lives. However, current treatment modalities, such as anesthetic and antipyretic analgesics, have limitations in terms of efficacy and side effects. Nanomedical technology offers a promising avenue to overcome these challenges and introduce new therapeutic mechanisms. This article reviews the recent research on nanomedicine analgesics, integrating analyses of neuroplasticity changes in neurons and pathways related to the transition from acute to chronic pain. Furthermore, it explores potential future strategies using nanomaterials, aiming to provide a roadmap for new analgesic development and improved clinical pain management. By leveraging nanotechnology, these approaches hold the potential to revolutionize pain treatment by delivering targeted and effective relief while minimizing side effects.

ObjectivesThe systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population.MethodsOur study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD.ResultsFollowing confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07–1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046).ConclusionsSII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.

IntroductionHyperuricemia (HUA) is a metabolic disorder caused by purine metabolism dysfunction in which the increasing purine levels can be partially attributed to seafood consumption. Perillae Folium (PF), a widely used plant in functional food, has been historically used to mitigate seafood-induced diseases. However, its efficacy against HUA and the underlying mechanism remain unclear. MethodsA network pharmacology analysis was performed to identify candidate targets and potential mechanisms involved in PF treating HUA. The candidate targets were determined based on TCMSP, SwissTargetPrediction, Open Targets Platform, GeneCards, Comparative Toxicogenomics Database, and DrugBank. The potential mechanisms were predicted via Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses. Molecular docking in AutoDock Vina and PyRx were performed to predict the binding affinity and pose between herbal compounds and HUA-related targets. A chemical structure analysis of PF compounds was performed using OSIRIS DataWarrior and ClassyFire. We then conducted virtual pharmacokinetic and toxicity screening to filter potential inhibitors. We further performed verifications of these inhibitors’ roles in HUA through molecular dynamics (MD) simulations, text-mining, and untargeted metabolomics analysis. ResultsWe obtained 8200 predicted binding results between 328 herbal compounds and 25 potential targets, and xanthine dehydrogenase (XDH) exhibited the highest average binding affinity. We screened out five promising ligands (scutellarein, benzyl alpha-D-mannopyranoside, elemol, diisobutyl phthalate, and (3R)-hydroxy-beta-ionone) and performed MD simulations up to 50 ns for XDH complexed to them. The scutellarein-XDH complex exhibited the most satisfactory stability. Furthermore, the text-mining study provided laboratory evidence of scutellarein’s function. The metabolomics approach identified 543 compounds and confirmed the presence of scutellarein. Extending MD simulations to 200 ns further indicated the sustained impact of scutellarein on XDH structure. ConclusionOur study provides a computational and biomedical basis for PF treating HUA and fully elucidates scutellarein's great potential as an XDH inhibitor at the molecular level, holding promise for future drug design and development.

In the service industry, highway toll collectors serve as a distinctive frontline workforce who frequently encounter mistreatment from customers. Unfortunately, these behaviors have not received the attention and resolution they deserve, resulting in significant physical and psychological stress for toll collectors and exacerbating turnover rates. The study highlights how customer mistreatment affects toll collectors’ turnover intentions by performing the sequential mediating roles of stress symptoms and affective commitment and assumes that neuroticism exacerbates the stress symptoms resulting from customer mistreatment based on affective events theory. The model was tested using data collected from 230 highway toll collectors in Zhuhai, China. All hypotheses received support. This study holds both theoretical and practical implications for future research.

Constructing three-dimensional (3D) bioprinted skin tissues that accurately replicate the mechanical properties of native skin and provide adequate oxygen and nutrient support remains a formidable challenge. In this study, we incorporated phosphosilicate calcium bioglasses (PSCs), a type of bioactive glass (BG), into the bioinks used for 3D bioprinting. The resulting bioink exhibited mechanical properties and biocompatibility that closely resembled those of natural skin. Utilizing 3D bioprinting technology, we successfully fabricated full-thickness skin substitutes, which underwent comprehensive evaluation to assess their regenerative potential in treating full-thickness skin injuries in rats. Remarkably, the skin substitutes loaded with PSCs exhibited exceptional angiogenic activity, as evidenced by the upregulation of angiogenesis-related genes in vitro and the observation of enhanced vascularization in wound tissue sections in vivo. These findings conclusively demonstrated the outstanding efficacy of PSCs in promoting angiogenesis and facilitating the repair of full-thickness skin wounds. The insights garnered from this study provide a valuable reference strategy for the development of skin tissue grafts with potent angiogenesis-inducing capabilities.

Summary: Background: Increasing evidence supports that antibodies can protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially in the airways, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) versus uncontrolled infection (TB) in nonhuman primates. Methods: In a case–control design, using non-parametric group comparisons with false discovery rate adjustments, we assessed antibodies in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to, two-, and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays. Findings: Macaques that developed LTBI (n = 36) had significantly increased airway and plasma IgA reactivities to specific arabinomannan (AM) motifs prior to Mtb infection compared to those that developed TB (n = 21; p