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Abstract Background We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. Results The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. Conclusion Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Abstract Protein complexes are fundamental to all cellular processes, so understanding their evolutionary history and assembly processes is important. Gene duplication followed by divergence is considered a primary mechanism for diversifying protein complexes. Nonetheless, to what extent assembly of present-day paralogous complexes has been constrained by their long evolutionary pathways and how cross-complex interference is avoided remain unanswered questions. Subunits of protein complexes are often stabilized upon complex formation, whereas unincorporated subunits are degraded. How such cooperative stability influences protein complex assembly also remains unclear. Here, we demonstrate that subcomplexes determined by cooperative stabilization interactions serve as building blocks for protein complex assembly. We further develop a protein stability-guided method to compare the assembly processes of paralogous complexes in cellulo. Our findings support that oligomeric state and the structural organization of paralogous complexes can be maintained even if their assembly processes are rearranged. Our results indicate that divergent assembly processes by paralogous complexes not only enable the complexes to evolve new functions, but also reinforce their segregation by establishing incompatibility against deleterious hybrid assemblies.

Melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) is a rare systemic autoimmune disease associated with a high rate of mortality attributable to rapidly progressive interstitial lung disease. MDA5-positive DM is often complicated by a typical rash and muscle weakness. Herein, we describe a 50-year-old woman who presented with worsening pulmonary symptoms with an absence of typical clinical characteristics. We also review the treatments and prognosis made in similar cases, highlighting that closer attention should be paid to patients presenting with atypical DM, particularly when clinical manifestations such as rash and muscle weakness are not apparent.

ABSTRACT: Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

Abstract Background To successfully replicate within the host cell, Toxoplasma gondii employs several mechanisms to overcome the host cell defenses and mitigate the harmful effects of the free radicals resulting from its own metabolic processes using effectors such as thioredoxin proteins. In this study, we characterize the location and functions of a newly identified thioredoxin in T. gondii, which was named Trx4. Methods We characterized the functional role of Trx4 in T. gondii Type I RH and Type II Pru strains by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The enzyme-catalyzed proximity labeling technique, the TurboID system, was employed to identify the proteins in proximity to Trx4. Results Trx4 was identified as a dense granule protein of T. gondii predominantly expressed in the parasitophorous vacuole (PV) and was partially co-localized with GRA1 and GRA5. Functional analysis showed that deletion of trx4 markedly influenced the parasite lytic cycle, resulting in impaired host cell invasion capacity in both RH and Pru strains. Mutation of Trx domains in Trx4 in RH strain revealed that two Trx domains were important for the parasite invasion. By utilizing the TurboID system to biotinylate proteins in proximity to Trx4, we identified a substantial number of proteins, some of which are novel, and others are previously characterized, predominantly distributed in the dense granules. In addition, we uncovered three novel proteins co-localized with Trx4. Intriguingly, deletion of trx4 did not affect the localization of these three proteins. Finally, a virulence assay demonstrated that knockout of trx4 resulted in a significant attenuation of virulence and a significant reduction in brain cyst loads in mice. Conclusions Trx4 plays an important role in T. gondii invasion and virulence in Type I RH strain and Type II Pru strain. Combining the TurboID system with CRISPR-Cas9 technique revealed many PV-localized proximity proteins associated with Trx4. These findings suggest a versatile role of Trx4 in mediating the processes that occur in this distinctive intracellular membrane-bound vacuolar compartment. Graphical Abstract

Abstract Background Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. Methods This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. Results During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566–3.008; P

Abstract Objective To analyse and discuss the association of gender differences with the risk and incidence of poststroke aphasia (PSA) and its types, and to provide evidence-based guidance for the prevention and treatment of poststroke aphasia in clinical practice. Data sources Embase, PubMed, Cochrane Library and Web of Science were searched from January 1, 2002, to December 1, 2023. Study selection Including the total number of strokes, aphasia, the number of different sexes or the number of PSA corresponding to different sex. Data extraction Studies with missing data, aphasia caused by nonstroke and noncompliance with the requirements of literature types were excluded. Data synthesis 36 papers were included, from 19 countries. The analysis of 168,259 patients with stroke and 31,058 patients with PSA showed that the risk of PSA was 1.23 times higher in female than in male (OR = 1.23, 95% CI = 1.19–1.29, P

Abstract Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.

Cadmium (Cd2+) is a non-essential and highly toxic element to all organic life forms, including plants and humans. In response to Cd stress, plants have evolved multiple protective mechanisms, such as Cd2+ chelation, vesicle sequestration, the regulation of Cd2+ uptake, and enhanced antioxidant defenses. When Cd2+ accumulates in plants to a certain level, it triggers a burst of reactive oxygen species (ROS), leading to chlorosis, growth retardation, and potentially death. To counteract this, plants utilize a complex network of enzymatic and non-enzymatic antioxidant systems to manage ROS and protect cells from oxidative damage. This review systematically summarizes how various elements, including nitrogen, phosphorus, calcium, iron, and zinc, as well as phytohormones such as abscisic acid, auxin, brassinosteroids, and ethylene, and signaling molecules like nitric oxide, hydrogen peroxide, and hydrogen sulfide, regulate the antioxidant system under Cd stress. Furthermore, it explores the mechanisms by which exogenous regulators can enhance the antioxidant capacity and mitigate Cd toxicity.

Abstract Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.

Abstract Background Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. Methods We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 − 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. Results As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89–6.71), Brazil (3.45, 95% CI: 1.62–7.00) and the United States (2.44, 95% CI: 1.62–3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. Conclusions The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients’ clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85–160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3–4.5) days. The median hospitalization expense for these patients was 3848 (3781–4145) USD. The median number of lymph node yielded was 10.5 (8–15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

With the aggravation of environmental pollution and the worldwide epidemic of infectious diseases, there is a higher demand for air filtration materials to intercept fine particulate matter and capture biological pollutants. Polypropylene (PP)/polycarbonate (PC) blends were melt blown and electrospun with polytetrafluoroethylene (PTFE) on their surfaces. The PP/PC/PTFE membranes structure with micro-nanostructure was constructed through the melt-blown layer with micron structure and the electrospun layer with the nanostructure. Carboxymethyl chitosan (CMCS) was loaded onto the surface of the PP/PC melt-blown layer. The synergistic effect of micro-nanostructure and CMCS can effectively capture PM2.5 and make the composite membrane have excellent antibacterial performance. The inhibition rates of PP/PC/PTFE composite membrane loaded with 5% CMCS against Staphylococcus aureus and Escherichia coli reached 81.54% and 86.1%, respectively. The filtration efficiency of PP/PC/PTFE composite membrane loaded with 5% CMCS is close to 100% for 0.25 μm particles, and the average filtration efficiency for 0.200–4.596 μm and 0.200–2.500 μm particles is 97.31% and 97.27%, respectively. After washing and drying five times, the corresponding inhibition rate only lost 16.52% and 4.24%. The micro/nano structure composite membrane prepared in this study has good antibacterial performance, high filtration efficiency, good stability, and is an excellent antibacterial high efficiency air filter. It provides a new idea for the preparation of air filter fiber composites.

In this study, a Ti3C2 MXene@g-C3N4 composite powder (TM-CN) was prepared by the ultrasonic self-assembly method and then loaded onto a carbon nanofiber membrane by the self-assembly properties of MXene for the treatment of organic pollutants in wastewater. The characterization of the TM-CN and the C-TM-CN was conducted via X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometer (FTIR) to ascertain the successful modification. The organic dye degradation experiments demonstrated that introducing an appropriate amount of Ti3C2 MXene resulted in the complete degradation of RhB within 60 min, three times the photocatalytic efficiency of a pure g-C3N4. The C-TM-CN exhibited the stable and outstanding photocatalytic degradation of the RhB solution over a wide range of pH values, indicating the characteristics of the photodegradation of organic pollutants in a wide range of aqueous environments. Furthermore, the results of the cyclic degradation experiments demonstrated that the C-TM-CN composite film maintained a degradation efficiency of over 85% after five cycles, thereby confirming a notable improvement in its cyclic stability. Consequently, the C-TM-CN composite film exhibits excellent photocatalytic performance and is readily recyclable, making it an auspicious eco-friendly material in water environment remediation.

Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.

BackgroundThe suggested threshold level of cardiac troponin T elevation after cardiac surgery is not very clear, and the values recommended by various guidelines and literature reports are quite different.MethodsIn this retrospective cohort study, we collected clinical data of patients who underwent heart surgery at Tsinghua University First Hospital between January 2015 and December 2022. Using the high-sensitivity cardiac troponin T levels (reference upper limit: 14 ng/L) measured at 1–3 days postoperation, the relationship between the cardiac troponin T level and the 30-day mortality risk was evaluated using Cox regression analysis.ResultsAmong the 3,128 patients included in this study, the types of operations mainly consisted of coronary artery bypass graft (CABG, 1,164, 37.2%), aortic valve replacement (AVR, 735, 23.5%), and other cardiac operations (1,229, 39.3%). Within 30 days postoperation, 57 patients (1.8%) died and 72 patients (2.3%) developed major vascular complications. In patients undergoing CABG or AVR, the cardiac troponin T threshold level measured within one day postoperation related to an increased 30-day mortality was determined to be 3,012 ng/L (95% CI: 1,435–3,578 ng/L), which is 218 times higher than the reference upper limit. In patients undergoing other cardiac operations, this threshold was 5,876 ng/L (95% CI: 2,458–8,119 ng/L), which is 420 times higher than the reference upper limit.ConclusionThe high-sensitivity cardiac troponin T level associated with an increased 30-day mortality risk after cardiac surgery is significantly higher than the current recommendations for defining clinically important perioperative myocardial injury.

Serine/arginine-rich (SR) proteins are key factors with important roles in constitutive and alternative splicing (AS) of pre-mRNAs. However, the role of SR splicing factors in the pathogenicity of T. gondii remains largely unexplored. Here, we investigated the role of splicing factor SR2, a homolog of Plasmodium falciparum SR1, in the pathogenicity of T. gondii. We functionally characterized the predicted SR2 in T. gondii by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The results showed that SR2 was localized in the nucleus and expressed in the tachyzoite and bradyzoite stages. In vitro studies including plaque formation, invasion, intracellular replication, egress and bradyzoite differentiation assays showed that deletion of SR2 in type I RH strain and type II Pru strains had no significant effect on the parasite growth and bradyzoite differentiation (p > 0.05). Interestingly, the disruption of SR2 in RH type I (p

This study explores a new type of nanofiber membrane using water-soluble polymer material, polyethylene glycol (PEG), as the main raw material. The membrane is prepared by combining PEG with polyvinyl pyrrolidone (PVP) and urushiol (UR) through electrospinning. The research findings demonstrate that the degradation rate of the nanofiber membrane can be controlled by adjusting the UR content, enabling the production of wound dressings that match the required healing time. Additionally, the addition of UR provides the nanofiber membrane with certain antimicrobial effects against Escherichia coli and Staphylococcus aureus. When combined with nano zinc oxide (ZnO), the antimicrobial effect of the nanofiber membrane reaches 99%. Furthermore, cytotoxicity experiments conducted on the nanofiber membrane meet the relevant standards. The results of this study provide a reliable option for researching and developing PEG materials with improved drug delivery effects. The nanofiber membrane possesses the characteristic of regulating degradation rate and shows potential for application in the field of wound healing, providing support for wound repair and tissue remodeling.

Osteoblasts are considered as a major factor contributing to bone development and mineralization, however, few studies have been done to establish and evaluate the primary cultured tibial osteoblast model of broiler chicks. Therefore, in the present study, two experiments were conducted to establish and evaluate the primary cultured tibial osteoblast model of broiler chicks. In experiment 1, osteoblasts were isolated from the tibia of one-day-old Arbor Acre male broiler chicks using the explant method and identified through the cell morphology, alkaline phosphatase (ALP) and alizarin red staining. Experiment 2 was carried out to evaluate the vitality and mineralization of primary cultured tibial osteoblasts of broilers on days 4, 8, 12, 16, 20, 24, 28 and 32 after incubation, respectively. The results from experiment 1 demonstrated that primary cultured tibial osteoblasts of broilers showed a spindle-shaped, triangular or polygonal morphology. More than 95% of the cells were stained blue-black after ALP staining, and mineralized nodules were formed after 4 days of continuous incubation. In experiment 2, lactate dehydrogenase (LDH) activity stayed at a relatively stabilized level although incubation time affected (P=0.0012) it during the whole culture period. Additionally, incubation time affected (P≤0.0001) the number and proportion of the area of mineralized nodules. They increased linearly and quadratically (P

Hydrogen energy has long been recognized as a clean alternative to conventional fossil fuels, which can be applied in a wide range of transportation and power generation applications. The rational design and engineering of high-performance and robust catalysts for hydrogen evolution reaction (HER) shows not a great significance but a challenge for efficient electrochemical water splitting. Herein, a new type of Ni-based Ni-ABDC precursor has been obtained, which leads to the formation of N-doped porous carbon nanomaterials uniformly coated with well-proportioned bimetallic AgNi alloys via a stepwise strategy. To their credit, all samples of AgNi/NC-X are structurally calcined from the pristine AgNi-ABDC-X by tuning the different concentration of AgNO3, which means all of them maintain the vermicelli-like morphology compared with Ni-ABDC. The series of AgNi/NC-X materials can be regarded as effective electrocatalysts for HER both in acidic and alkaline media, but an acid-leaching phenomenon is observed. Among them, the as-prepared AgNi/NC-2 exhibits a low overpotential of 103 mV at the current density of 10 mA cm−2 and decent durability with a high retention rate of 90.9% after 10 h in 1.0 mol L−1 KOH electrolyte. The compelling HER properties of AgNi/NC-2 can be attributed to the synergistic effect between the hierarchical carbon materials, partial N-doping and abundant AgNi alloys. Meanwhile, this study provides a practicable method for the development of efficient HER electrocatalysts for energy applications, which can be conveniently prepared through the reasonable introduction of active components in the crystalline inorganic-organic precursors.

Abstract Background Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. Results The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. Conclusions The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.

The shortage of water resources and the aggravation of water pollution have become global environmental problems. The improvement of the separation performance and flux is still a key challenge that restrict the preparation of high-performance filtration membrane. The gradient structure fibrous membranes were designed and prepared using electrospinning nanofiber and polypropylene/low-melt- point polyester (PP/LPET) micro-fibrous and reinforced via needle-punching and hot-pressing. And the as-prepared membrane was functionalized and directly decorated by dopamine copolymerizes. The novel gradient membrane turned from a hydrophobic state to hydrophilic state, and had excellent mechanical and water transmission properties. Mostly importantly, the as-prepared hydrophilic gradient membranes showed durable oil-fouling repellency and the separation efficiency of oil/water mixture approximate 99% and the flux reach 10,278 ± 1512 L m−2 h−1. This method provides a feasible solution to overcome the high filtration resistance of electrospinning nanofiber membrane, as well as for the preparation of low-cost and high-performance composite membranes and structural regulation of functional membranes.

Abstract There are many trillions of bacteria in the gastrointestinal microbiome (GM). Their ecological dysregulation can contribute to the development of certain neurodegenerative diseases, including Alzheimer's disease (AD). AD is common dementia and its incidence is increasing year by year. However, the relationship between GM and AD is unclear. Therefore, this review discusses the relationship between GM and AD, elaborates on the possible factors that can affect this relationship through the inflammation of the brain induced by blood−brain damage and accumulation of amyloid deposit, and proposes feasible ways to treat AD through GM‐related substances, such as probiotics, Mega‐3, and gut hormones, including their shortcomings as well.

Protein phosphorylation and dephosphorylation are essential aspects of biology. Wang et al., report that Toxoplasma gondiiprotein phosphatase 2A (PP2A) mediated dephosphorylation is critical for starch metabolism and bradyzoite differentiation.

Photoelectrodes constructed with photoactive materials are of great significance for the performance of photoelectrochemical (PEC) sensors. In this study, a facile and efficacious non-enzymatic glucose sensor based on the Cu2O/TiO2 heterojunction was successfully constructed for quantitative determination of glucose concentration. The Cu2O/TiO2 heterojunction was generated by first obtaining TiO2 nanofibers via electrostatic spinning and high-temperature calcination, and then synthesizing Cu2O nanoparticles via a one-step hydrothermal reaction. By introducing the narrow band gap semiconductor Cu2O, the defect that pure TiO2 could not absorb visible light was improved, resulting in the improved photoelectrochemical performance of the composite material compared to the single component semiconductor. The sensor exhibited favorable PEC non-enzymatic glucose sensing performance under simulated sunlight irradiation with a wide linear response range from 1 mM to 14 mM (R2 = 0.9991) and a low detection limit of 14.4 μM (S/N = 3), along with good selectivity, stability and reproducibility. This also provided more ideas and possibilities for preparing photoelectrode materials by constructing heterojunctions.

The bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) signaling pathways play an important role in regulation of bone formation and development, however, it remains unclear that the effect of dietary different levels of non-phytate phosphorus (NPP) on these signaling pathways and their correlations with bone phosphorus (P) retention and bone development in broilers. Therefore, this experiment was conducted to investigate the effect of dietary P supplementation on BMP and MAPK signaling pathways and their correlations with bone P retention and bone development in broilers. A total of 800 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 5 treatments with 8 replicates in a completely randomized design. The 5 treatments of dietary NPP levels were 0.15, 0.25, 0.35, 0.45 and 0.55% or 0.15, 0.22, 0.29, 0.36 and 0.43% for broilers from 1 to 21 days of age or 22 to 42 days of age, respectively. The results showed that extracellular signal-regulated kinase 1 (ERK1) mRNA expression in the tibia of broilers on days 14 and 28, phosphorylated-ERK1 (p-ERK1) on day 14, and BMP2 protein expression on days 28 and 42 decreased linearly (P

Objectives Understanding the occupational characteristics of patients is not only related to patients' life and health, but also conducive to improving their happiness. However, there were no studies that had been conducted on the relationship between occupation characteristic and postoperative recovery in patients with spinal fractures. The purpose of this study was to explore the relationship between the occupation characteristics of patients with thoracolumbar fracture and the characteristics of disease injury, treatment, and recovery so as to reduce the incidence and improve postoperative rehabilitation. Methods Patients (n = 719) with thoracolumbar fractures were recruited. Patients were grouped according to the characteristic of occupations: unemployed group (n = 299), white‐collar worker group (n = 20), and blue‐collar worker group (n = 400). Data were collected, including the characteristics, injury and treatment information, and the recovery records for 1 year after operation. One‐way ANOVA analysis, χ2 test, and binary logistic regression analysis was used to explore the relationship among these factors. Results Male, high‐falling injuries and single segment injury (mainly T 11, T 12 and L2) were common in patients with thoracolumbar fractures, especially in the blue‐collar worker group (70.8%, 78.3%, and 85.4%). Compared with the unemployed group, the patients in the white‐collar worker group and blue‐collar worker group had a higher proportion of young patients, a higher height and weight, a lesser rate of hypertension or diabetes. One week after injury, 73.4% of patients underwent surgery, with the blue‐collar worker group accounted for the largest proportion. One month after surgery, 77.1% of patients were able to get out of bed, with the white‐collar worker group accounted for the largest proportion. In the postoperative recovery information, patients in the blue‐collar worker group were more likely to have severe low back pain (OR = 2.023, 95% CI: 1.440‐2.284) and pain‐disturbed sleep (OR = 2.287, 95% CI: 1.585‐3.299) than those who in the unemployed group. Conclusions Blue‐collar workers, with a high risk of thoracolumbar fracture, have a higher incidence of low back leg pain and pain‐disturbed sleep in the recovery after thoracolumbar fracture surgery, and this requires more attention.

AIM: To perform a quantitative analysis of the peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness changes in patients with early stage of diabetic retinopathy (DR). METHODS: In this case-control study, swept-source optical coherence tomography angiography (SS-OCTA) imaging was used to examine diabetic and age-matched healthy subjects. The optic disc HD 6×6 mm2 blood flow imaging scan mode was selected. Automatic software was used to measure the peripapillary VD, capillary vessel density (CVD), and RNLF in an optic nerve head (ONH) filed based on the Garway-Heath map. In addition, the correlation between peripapillary VD, CVD, and RNFL was further investigated. RESULTS: The cohort consisted of 32 healthy individuals and 72 patients with diabetes (34 eyes with no DR and 38 eyes with mild-moderate NPDR). Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions (P

ObjectiveTo assess the computed tomography (CT) and magnetic resonance (MR) imaging characteristics of soft tissue rhabdoid tumors (RT) and compare them with those of rhabdomyosarcoma (RMS).MethodsWe conducted a retrospective analysis of 49 pediatric patients from 2011 to 2022, comprising 16 patients with soft tissue RT and 33 patients with RMS who underwent CT or MRI scans. Key imaging features, as well as clinical and pathological data, were compared between the two groups. The multivariate logistic regression analysis was used to determine independent differential factors for distinguishing soft tissue RT from RMS, and the model was established. The final prediction model was visualized by nomograms and verified internally by using a bootstrapped resample 1,000 times. The diagnostic accuracy of the combined model was assessed in terms of discrimination, calibration, and clinical utility.ResultsAge, sex, number of lesions, and primary locations were similar in both groups. The imaging characteristics, including margin, calcification, surrounding blood vessels, and rim enhancement, were associated with the two groups of soft tissue tumors, as determined by univariate analysis (all p

Abstract The photocatalytic transformation of carbon dioxide (CO2) into carbon‐based fuels or chemicals using sustainable solar energy is considered an ideal strategy for simultaneously alleviating the energy shortage and environmental crises. However, owing to the low energy utilization of sunlight and inferior catalytic activity, the conversion efficiency of CO2 photoreduction is far from satisfactory. In this study, a MOF‐derived hollow bimetallic oxide nanomaterial is prepared for the efficient photoreduction of CO2. First, a unique ZIF‐67‐on‐InOF‐1 heterostructure is successfully obtained by growing a secondary Co‐based ZIF‐67 onto the initial InOF‐1 nanorods. The corresponding hollow counterpart has a larger specific surface area after acid etching, and the oxidized bimetallic H‐Co3O4/In2O3 material exhibits abundant heterogeneous interfaces that expose more active sites. The energy band structure of H‐Co3O4/In2O3 corresponds well with the photosensitizer of [Ru(bpy)3]Cl2, which results in a high CO yield of 4828 ± 570 µmol h−1 g−1 and stable activity over a consecutive of six runs, demonstrating adequate photocatalytic performance. This study demonstrates that the rational design of MOF‐on‐MOF heterostructures can completely exploit the synergistic effects between different components, which may be extended to other MOF‐derived nanomaterials as promising catalysts for practical energy conversion and storage.

The aim of the study was to investigate whether phosphorus (P) transporters, type IIb sodium-dependent phosphate cotransporter (NaP-IIb) and inorganic phosphate transporter 2 (PiT2), were directly involved in P absorption across primary cultured duodenal epithelial cell monolayers of chick embryos. The siRNAs against NaP-IIb or PiT2 were designed, synthesized and transfected into primary cultured duodenal epithelial cells of chick embryos. Then, the inhibitory efficiency of siRNAs against NaP-IIb or PiT2 was analyzed, and the most efficacious siRNAs were selected to be used for subsequent P absorption experiments. Briefly, primary cultured duodenal epithelial cells of chick embryos were transfected with either NaP-IIb or PiT2 siRNAs and grown in confluent monolayers on transwell plates. The untransfected or transfected cell monolayers were then incubated in an uptake medium containing 0 or 0.25 mmol L–1 of P as KH2PO4 to measure the P absorption across duodenal epithelial cell monolayers. The results showed that among the siRNAs designed, si-1372 and si-890 were demonstrated to be the most effective in inhibiting the NaP-IIb and PiT2 expressions, respectively. Supplemental P increased (P=0.065) the protein abundance of PiT2 and enhanced (P

Abstract Objectives To find out the reasons why patients still need to use rescue analgesics frequently after gastrointestinal tumor surgery under the patient-controlled intravenous analgesia (IV-PCA), and the different abdominal surgery patients using the difference of analgesics. Methods A total of 970 patients underwent abdominal operation for gastrointestinal tumors were included. According whether patients used dezocine frequently for rescue analgesics within 2 days after surgery, they assigned into two groups: RAN group (Patients who did not frequently use rescue analgesia, 406 cases) and RAY group (Patients who frequently used rescue analgesia, 564 cases). The data collected included patient’s characteristics, postoperative visual analogue scale (VAS), nausea and vomiting (PONV), and postoperative activity recovery time. Results No differences were observed in the baseline characteristics. Compared with the RAN group, patients in the RAY group had a higher proportion of open surgery, upper abdominal surgery, VAS score at rest on the first 2 days after surgery and PONV, and a slower recovery of most postoperative activities. Under the current use of IV-PCA background, the proportion of rescue analgesics used by patients undergoing laparotomy and upper abdominal surgery was as high as 64.33% and 72.8%, respectively. Regression analysis showed that open surgery (vs laparoscopic surgery: OR: 2.288, 95% CI: 1.650–3.172) and the location of the tumor in the upper abdomen (vs lower abdominal tumor: OR: 2.738, 95% CI: 2.034–3.686) were influential factors for frequent salvage administration. Conclusions In our patient population, with our IV-PCA prescription for postoperative pain control, patient who underwent open upper abdominal surgery required more rescue postoperative analgesia.

The precise control of free auxin (indole-3-acetic acid, IAA) gradient, which is orchestrated by biosynthesis, conjugation, degradation, hydrolyzation, and transport, is critical for all aspects of plant growth and development. Of these, the GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetase family, pivotal in conjugating IAA with amino acids, has garnered significant interest. Recent advances in understanding GH3-dependent IAA conjugation have positioned GH3 functional elucidation as a hot topic of research. This review aims to consolidate and discuss recent findings on (i) the enzymatic mechanisms driving GH3 activity, (ii) the influence of chemical inhibitor on GH3 function, and (iii) the transcriptional regulation of GH3 and its impact on plant development and stress response. Additionally, we explore the distinct biological functions attributed to IAA-amino acid conjugates.

Abstract Background To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA). Methods Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis. Results There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24th h, resting: 1,1; movement: 3,2. 48th h, resting: 0,1; movement: 2,1.) and PCEA (24th h, resting: 0,1; movement: 2,1. 48th h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24th h, resting: 2.5,2; movement: 4,2. 48th h, resting: 1.5,1.75; movement: 3,1.) (all p

Abstract Currently, there is no effective therapy for traumatic brain injury (TBI). Therefore, this study was conducted to determine the protective effect of Lu Tong Ke Li (LTKL), a Chinese medicine, for TBI in experimental animals. The TBI rat model was induced using the modified Feeney's protocol. The rats were divided into four groups: Sham group, Control group, LTKL lower‐dose group (LTL, 2 g/kg/day, p.o.), and LTKL higher‐dose group (LTH, 4 g/kg/day, p.o.). The Neurological Severity Score (NSS) was used to examine neurological function. Magnetic resonance imaging was performed to check the brain tissue lesions in rats. Cell apoptosis in the damaged area was evaluated using the Terminal deoxynucleotidyl transferase deoxy‐UTP‐nick end labeling assay. Reverse‐transcription polymerase chain reaction was used to investigate the expression of inflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), interleukin 1β (IL‐1β), and interleukin 10 (IL‐10). The TBI rat model was successfully constructed. Neurological function was enhanced at 14, 21, and 28 days post TBI in the LTH groups, indicated by gradually decreased NSS scores. Administration of LTH led to fewer brain defects in the damaged area, and the number of apoptosis cells in the brain injury area markedly decreased. LTKL treatment led to upregulation of IL‐10 expression and downregulation of TNF‐α and IL‐1β expressions at the molecular level. LTKL can improve the neurobehavior of TBI. The neuroprotective effect was probably related to regulation of inflammation cytokines. Our results provide crucial evidence of the potentially useful application of LTKL in the therapy of TBI in clinic practice in the future.

BackgroundEndoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC).MethodsPTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented.ResultsIn total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1–30) and 1.0 ± 1.8 (range, 0–12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner’s syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred.ConclusionThe five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.

BackgroundBreathing exercises improve oxidative stress in healthy young adults and patients with diabetes, hypertension, and chronic obstructive pulmonary disease. Furthermore, the mechanism of respiratory intervention is controversial. Therefore, in this meta-analysis, we aimed to systematically evaluate the effects of breathing exercises on oxidative stress biomarkers in humans and provide evidence for the clinical application of breathing exercises.MethodsThe Embase, PubMed, Cochrane Library, Web of Science, CNKI, and WANFANG databases were searched for studies about the effects of breathing exercises on human oxidative stress levels, with no restraints regarding time, race, or language. The experimental group included various breathing exercises, and the outcome index included malondialdehyde, superoxide dismutase, and glutathione, nitric oxide, vitamin C, or total antioxidant capacity levels from a randomized controlled trial. Data were extracted by more than two authors and reviewed by one author.ResultsTen studies were included from five countries. Data from patients with no disease, chronic obstructive pulmonary disease, hypertension, or diabetes were included. Participants who performed breathing exercises had greater changes in the included biomarkers than those who did not, suggesting that these biomarkers can be used to evaluate oxidative stress after respiratory interventions.ConclusionBreathing exercises increased SOD and GSH activities and decreased MDA content.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337119, identifier CRD42022337119.

BackgroundHuman adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types responsible for ARTI outbreaks remains obscure in China.MethodsA systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015.ResultsA total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children ConclusionsThis study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings.

ABSTRACT The analysis of the subcellular localization and function of dense granule proteins (GRAs) is of central importance for the understanding of host-parasite interaction and pathogenesis of Toxoplasma gondii infection. Here, we identified 15 novel GRAs and used C-terminal endogenous gene tagging to determine their localization at the intravacuolar network (IVN), parasitophorous vacuole (PV), or PV membrane (PVM) in the tachyzoites and at the periphery of the bradyzoites-containing cysts. The functions of the 15 gra genes were examined in type I RH strain and 5 of these gra genes were also evaluated in the cyst-forming type II Pru strain. The 15 novel gra genes were successfully disrupted by using CRISPR-Cas9 mediated homologous recombination and the results showed that 13 gra genes were not individually essential for T. gondii replication in vitro or virulence in mice during acute and chronic infection. Intriguingly, deletion of TGME49_266410 and TGME49_315910 in both RH and Pru strains decreased the parasite replication in vitro and attenuated its virulence, and also reduced the cyst-forming ability of the Pru strain in mice during chronic infection. Comparison of the transcriptomic profiles of the 15 gra genes suggests that they may play roles in other life cycle stages and genotypes of T. gondii. Taken together, our findings improve the understanding of T. gondii pathogenesis and demonstrate the involvement of two novel GRAs, TGME49_266410 and TGME49_315910, in the parasite replication and virulence. IMPORTANCE Dense granule proteins (GRAs) play important roles in Toxoplasma gondii pathogenicity. However, the functions of many putative GRAs have not been elucidated. Here, we found that 15 novel GRAs are secreted into intravacuolar network (IVN), parasitophorous vacuole (PV), or PV membrane (PVM) in tachyzoites and are located at the periphery of the bradyzoite-containing cysts. TGME49_266410 and TGME49_315910 were crucial to the growth of RH and Pru strains in vitro. Deletion of TGME49_266410 and TGME49_315910 attenuated the parasite virulence in mice. However, disruption of other 13 gra genes did not have a significant impact on the proliferation and pathogenicity of T. gondii in vitro or in vivo. The marked effects of the two novel GRAs (TGME49_266410 and TGME49_315910) on the in vitro growth and virulence of T. gondii are notable and warrant further elucidation of the temporal and spatial dynamics of translocation of these two novel GRAs and how do they interfere with host cell functions.

Diabetes mellitus is an independent risk factor for ischemic stroke. Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes. Stellate ganglion block can effectively regulate the inflammatory response. Therefore, it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects. In this study, we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks. The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats. Subsequently, we performed left stellate ganglion block with 1% lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion. Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content. It also improved the recovery of neurological function, increased 28-day survival rate, inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats. However, injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block, whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect. We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke. These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway. We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.

Abstract This study aimed to explore the possible target and mechanism of the wheel treadmill (WTM) test for motor function recovery of spinal cord injury (SCI). Rats were divided into sham, control and WTM groups to establish an SCI mode. Rats in the WTM group were trained on the WTM test, and Basso–Beattie–Bresnahan (BBB) scores were determined. The samples were collected, and mRNA sequencing was conducted to determine the changes in gene expression. The coexpressed genes were screened to construct a protein–protein interaction (PPI), followed by the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology function enrichment analysis, and the differentially expressed genes (DEGs) volcano map and hub gene expression heat map were constructed using R language. The BBB scores in the control and WTM groups increased with time, with the WTM group scoring higher than the control group. The results of rat spinal cord tissue sequencing showed that a total of 1679 DEGs were screened in the sham and control groups; 928 DEGs and 731 overlapping genes were screened in the WTM and control groups. The key genes were identified by PPI analysis. One hundred and thirty‐three genes were found to be overlapping by combined analysis of spinal cord sequencing data and BBB scores of rats at Week 7. The top 10 DEGs from high to low were Tyrobp, Rac2, Cd68, C1qb, Aif1, Cd74, Spi1, Fcer1g, RT1‐DA, and Ccl4. The terms with the highest enrichment scores were microglia‐mediated positive regulation of cytotoxicity and major histocompatibility complex class II protein complexes. Treatment with the WTM test promotes recovery of motor function after SCI in rats by modulating intercellular communication and immune function.

In order to prepare a new high-performance and flexibility stab-resistant composite material, one type of high-toughness and high-strength hydrogel is combined with aramid fabric. In this paper, the nanocomposite (NC) hydrogels are prepared using Pluronic F127 Diacrylate (PF127DA) as the crosslinking agent, acrylamide as the monomer and nano-silica as nano additive. The influence of the addition amount of nano-silica on the toughness and strength of nano-composite hydrogels is discussed. The strength and toughness of the NC hydrogels with nano silica are higher than that of the acrylamide hydrogel without nano particles. The NC hydrogel with the best strength is made as a composite with aramid fabric and the effect of nanocomposite hydrogel on the stab resistance of the stab-resistant composite material is studied. The research shows that the stab resistance performance of the composite material prepared by aramid fabric and nanocomposite hydrogel is effectively improved in comparison with aramid fabric, and the yarn pulling force is also improved. The composite material with high stab resistance can be used as the stab-resistant layer of armor, cut-resistant gloves and stab-resistant base material of shoes. This work provided a possibility for preparing a kind of lightweight composite material with high stab resistance.

With the rapid development of wearable electronic products and smart devices, there is an urgent need to develop efficient electromagnetic interference (EMI)shielding materials to eliminate the resulting radiation pollution. Herein, hydrophobic and multi-responsive conductive composite film with core-shell structure and sandwich structure are constructed via simple in-situ polymerization and dip coating methods. The thin silicone coating can enhance the bonding fastness of the substrate and the conductive functional layer and endow the composite film excellent waterproof performance. The composite film with a thickness of 45 μm exhibits outstanding electrical conductivity of 62.15 S/cm and EMI shielding effectiveness (EMI SE) of 37.71 dB. Surprisingly, the composite film also exhibits good waterproof performance and excellent electro-optical thermal response, and has good stability in complex environments. This work proves the advantages of constructing multiple conductive interfaces inside the nanofiber film, and provides a new preparation strategy for efficient multifunctional shielding materials, which is expected to be widely used in the next generation of wearable electronic devices and wearable smart clothing.

Objective. To evaluate the analgesic efficacy and safety of different does of intravenous ibuprofen (IVIB) in the treatment of postoperative acute pain. Methods. Patients with an intravenous (IV) patient-controlled analgesia device after abdominal or orthopedic surgery were randomly divided into placebo, IVIB 400 mg, and IVIB 800 mg groups. The first dosage of study medicines was given intravenously 30 minutes (min) before surgery ended, followed by six hours (h) intervals for a total of eight doses following surgery. The demographic characteristics and procedure data, cumulative morphine consumption, the visual analog scale (VAS), the area under the curve (AUC) of VAS, patient satisfaction score (PSS), the rates of treatment failure (RTF), and adverse events (AEs) and serious adverse event (SAEs) were recorded during the period of trial. Result. A total of 345 patients were enrolled in the full analysis set (FAS), and of 326 participants were valid data set (VDS). Demographic characteristics, disease features, and medical history of patients were not significantly different between groups. Total morphine consumption of the IVIB 400 mg group (11.14 ± 7.14 mg; P = 0.0011) and the IVIB 800 mg group (11.29 ± 6.45 mg; P = 0.0014) was significantly reduced compared with the placebo group (14.51 ± 9.19 mg) for 24 h postoperatively, there was no significant difference between the IVIB 400 mg and IVIB 800 mg groups (P = 0.9997). The placebo group had significantly higher VAS and the AUCs of VAS than those in the IVIB 400 mg and the IVIB 800 mg groups at rest and movement for 24 h postoperatively (P 0.05). RTF was slightly higher in the placebo group than IVIB 400 mg group and 800 mg group, and no statistical significance (P 0.05) were not different among the three groups. Conclusion. Intermittent IV administration of ibuprofen 400 mg or 800 mg within 24 h after surgery in patients undergoing abdominal and orthopedic surgery significantly decreased morphine consumption and relieved pain, without increasing the incidence of AEs.

Background:. Exosomal proteins from cancer cells are becoming new biomarkers for cancer monitoring and efficacy evaluation. However, their biological function and molecular mechanism underlying tumor metastasis are largely unknown. Methods:. Bioinformatic methods such as bulk gene expression analysis, single-cell RNA sequencing data analysis, and gene set enrichment analysis were employed to identify metastasis-associated proteins. The in vitro and in vivo experiments were used to investigate the function of RAB13 in HCC metastasis. Results:. We identified RAB13 as one of the critical regulators of metastasis in HCC-derived exosomes for the first time. In vitro, the invasiveness of HCC cell lines could be attenuated by RAB13 silence. In vivo, tumor size and proportion of high-grade lung metastatic nodule could be reduced in the mice with orthotopic transplantation of tumors and intravenously injected with exosomes derived from MHCC97H cell with RAB13 silence (si-RAB13-Exo), as compared with those without RAB13 silence (si-NC-Exo). Moreover, in si-RAB13-Exo group, circulating tumor cell counts were decreased at the third, fourth, and fifth weeks after orthotopic transplantation of tumors, and MMP2 (matrix metalloproteinase 2)/TIMP2 (tissue inhibitor of metalloproteinases 2) ratio was also significantly decreased. In addition, RAB13 expression was also associated with VEGF levels, microvessel density, and tube formation of vascular endothelial cells by both in vitro and in vivo models, indicating that RAB13 was associated with angiogenesis in HCC. Conclusions:. We have demonstrated exosomal RAB13 as a potential regulator of metastasis for HCC by in silico, in vitro, and in vivo methods, which greatly improve our understanding of the functional impact of exosomal proteins on HCC metastasis.

Summary: The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.