Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial.

Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.

Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.

SETD2 is the only enzyme responsible for transcription-coupled histone H3 lysine 36 trimethylation (H3K36me3). Mutations in SETD2 cause human diseases including cancer and developmental defects. In mice, Setd2 is essential for embryonic vascular remodeling. Given that many epigenetic modifiers have recently been found to possess noncatalytic functions, it is unknown whether the major function(s) of Setd2 is dependent on its catalytic activity or not. Here, we established a site-specific knockin mouse model harboring a cancer patient-derived catalytically dead Setd2 (Setd2-CD). We found that the essentiality of Setd2 in mouse development is dependent on its methyltransferase activity, as the Setd2CD/CD and Setd2-/- mice showed similar embryonic lethal phenotypes and largely comparable gene expression patterns. However, compared with Setd2-/-, the Setd2CD/CD mice showed less severe defects in allantois development, and single-cell RNA-seq analysis revealed differentially regulated allantois-specific 5' Hoxa cluster genes in these two models. Collectively, this study clarifies the importance of Setd2 catalytic activity in mouse development and provides a new model for comparative study of previously unrecognized Setd2 functions.

Viral aptamer screening and aptamer-based biosensors for virus detection: A review.

Virus-induced infectious diseases have a detrimental effect on public health and exert significant influence on the global economy. Therefore, the rapid and accurate detection of viruses is crucial for effectively preventing and diagnosing infections. Aptamer-based detection technologies have attracted researchers' attention as promising solutions. Aptamers, small single-stranded DNA or RNA screened via systematic evolution of ligands by exponential enrichment (SELEX), possess a high affinity towards their target molecules. Numerous aptamers targeting viral marker proteins or virions have been developed and widely employed in aptamer-based biosensors (aptasensor) for virus detection. This review introduces SELEX schemes for screening aptamers and discusses distinctive SELEX strategies designed explicitly for viral targets. Furthermore, recent advances in aptamer-based biosensing methods for detecting common viruses using different virus-specific aptamers are summarized. Finally, limitations and prospects associated with developing of aptamer-based biosensors are discussed.

Red blood cell folate level is associated with periodontitis in American adults: results from the NHANES 2009-2014.

BACKGROUND: Red blood cell (RBC) folate is an indicator of long-term folate nutrition. Whether there is an association between RBC folate and periodontitis is unclear. This study aimed to use the NHANES database to determine whether RBC folate is associated with moderate/severe periodontitis. METHODS: A cross-sectional analysis of 10,151 participants in the NHANES database from 2009 to 2014 was performed. Multivariate logistic regression was used to analyze the independent relationship between RBC folate and moderate/severe periodontitis. The generalized additive model (GAM), restricted cubic splines (RCS), smooth curve fitting, and threshold effect analysis were used to explore the dose-response relationship and the potential nonlinear relationship between RBC folate and periodontitis. Finally, subgroup analysis and interaction tests were performed to determine the effect of covariates on the relationship between RBC folate and moderate/severe periodontitis. RESULTS: After adjusting for all confounders, there was a negative association between RBC folate concentration and moderate/severe periodontitis. The lowest fraction Q1 (< 360 ng/mL) of RBC folate concentration was used as the reference group, multivariable-adjusted ORs and 95% CIs of the second (360-463 ng/mL), third (464-569 ng/mL), fourth (570-732 ng/mL), and the highest quintile (> 733 ng/mL) categories were 0.88 (0.77, 1.01), 0.83 (0.72, 0.96), 0.77 (0.67, 0.90), 0.65 (0.56, 0.77) respectively. Additionally, a threshold nonlinear association was found between RBC folate (ng/mL) log2 transformation and moderate/severe periodontitis. CONCLUSION: This cross-sectional study revealed a negative relationship between RBC folate and moderate/severe periodontitis within a certain threshold range. Dentists and policymakers should pay closer attention to oral hygiene and health care for people with low or high RBC folate levels. Further causal and longitudinal research mechanisms are needed to validate our findings.

Intracellular Gelation-Mediated Living Bacteria for Advanced Biotherapeutics in Mouse Models.

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

Prolyl hydroxylase domain enzyme PHD2 inhibits proliferation and metabolism in non-small cell lung cancer cells in HIF-dependent and HIF-independent manners.

Prolyl hydroxylase domain protein 2 (PHD2) is one of the intracellular oxygen sensors that mediates proteasomal degradation of hypoxia-inducible factor (HIF)-α via hydroxylation under normoxic conditions. Because of its canonical function in the hypoxia signaling pathway, PHD2 is generally regarded as a tumor suppressor. However, the effects of PHD2 in tumorigenesis are not entirely dependent on HIF-α. Based on analysis of data from the Cancer Genome Atlas (TCGA) database, we observed that the expression of PHD2 is upregulated in non-small cell lung cancer (NSCLC), which accounts for approximately 80-85% of lung cancers. This suggests that PHD2 may play an important role in NSCLC. However, the function of PHD2 in NSCLC remains largely unknown. In this study, we established PHD2-deficient H1299 cells and PHD2-knockdown A549 cells to investigate the function of PHD2 in NSCLC and found that PHD2 suppresses cell proliferation and metabolism but induces ROS levels in human NSCLC cells. Further results indicated that the function of PHD2 in NSCLC is dependent on its enzymatic activity and partially independent of HIF. Moreover, we performed RNA-sequencing and transcriptomic analysis to explore the underlying mechanisms and identified some potential targets and pathways regulated by PHD2, apart from the canonical HIF-mediated hypoxia signaling pathway. These results provide some clues to uncover novel roles of PHD2 in lung cancer progression.

Reductant-independent oxidative cleavage of cellulose by a novel marine fungal lytic polysaccharide monooxygenase.

Among the enzymes derived from fungus that act on polysaccharides, lytic polysaccharide monooxygenase (LPMOs) has emerged as a new member with complex reaction mechanisms and high efficiency in dealing with recalcitrant crystalline polysaccharides. This study reported the characteristics, structure, and biochemical properties of a novel LPMO from Talaromyces sedimenticola (namely MaLPMO9K) obtained from the Mariana Trench. MaLPMO9K was a multi-domain protein combined with main body and a carbohydrate-binding module. It was heterologously expressed in E. coli for analyzing peroxidase activity in reactions with the substrate 2,6-DMP, where H2O2 serves as a co-substrate. Optimal peroxidase activity for MaLPMO9K was observed at pH 8 and 25 °C, achieving the best Vmax value of 265.2 U·g-1. In addition, MaLPMO9K also demonstrated the ability to treat cellulose derivatives, and cellobiose substrates without the presence of reducing agents.

Hepatitis B infection is associated with periodontitis: the national health and nutrition examination survey (2009-2014).

BACKGROUND: Current research has been inconclusive regarding whether hepatitis B infection is associated with an increased risk of periodontitis. This study aims to test the null hypothesis that no association exists between hepatitis B infection and an increased risk of periodontitis using the National Health and Nutrition Examination Survey (2009-2014). METHODS: We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of the prevalence of periodontitis in patients with and without hepatitis B infection. Participants who had tested for hepatitis B and periodontitis were included. The included participants were divided into no/mild periodontitis and moderate/severe periodontitis groups according to their periodontal status. The association between hepatitis B infection and chronic periodontitis was evaluated by multivariable regression analyses adjusting for age, gender, race/ethnicity, education level, income-to-poverty ratio, smoking, alcohol, BMI, ALT, AST, creatinine, hypertension, and diabetes. RESULTS: A total of 5957 participants were included and divided into two groups: inactive periodontitis group (n = 3444) and active periodontitis group (n = 2513). The results showed that participants with hepatitis B had a higher risk of periodontitis. After adjusting for covariables, adults with hepatitis B infection were 38% more likely to have periodontitis compared to those without hepatitis B infection (95% Confidence Interval [CI]:1.085-1.754). CONCLUSIONS: In general, the results suggest that CHB is positively associated with the more severe periodontitis. These results suggest that people with hepatitis B infection should take good periodontal care measures to avoid the occurrence and development of periodontitis.

Cell-SELEX and application research of a DNA aptamer against esophageal squamous cell carcinoma (ESCC) cell line TE-1.

Esophageal cancer is a common cancer with high morbidity and mortality that severely threatens the safety and quality of human life. The strong metastatic nature of esophageal cancer enables it to metastasize more quickly and covertly, making it difficult for current diagnostic and treatment methods to achieve efficient early screening, as well as timely and effective treatment. As a promising solution, nucleic acid aptamers, a kind of special single-stranded DNA or RNA oligonucleotide selected by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, can specifically bind with different molecular targets. In this paper, random DNA single-stranded oligonucleotides were used as the initial library. Using TE-1 cells and HEEC cells as targets, specific binding sequences were selected by 15 rounds of the cell-SELEX method, and the aptamer sequence that binds to TE-1 cells with the most specificity was obtained and named Te4. The Te4 aptamer was further validated for binding specificity, binding affinity, type of target, in vitro cytotoxicity when conjugated with DOX(Te4-DOX), and in vivo distribution. Results of in vitro validation showed that Te4 has outstanding binding specificity with a Kd value of 51.16 ± 5.52 nM, and the target type of Te4 was preliminarily identified as a membrane protein. Furthermore, the cytotoxicity experiment showed that Te4-DOX has specific cytotoxicity towards cultured TE-1 cells. Finally, the results of the in vivo distribution experiment showed that the Te4 aptamer is able to specifically target tumor regions in nude mice, showing great potential to be applied in future diagnosis and targeted therapy of esophageal cancer.

From biogenesis to aptasensors: advancements in analysis for tumor-derived extracellular vesicles research.

Extracellular vesicles (EVs) are enclosed by a nanoscale phospholipid bilayer membrane and typically range in size from 30 to 200 nm. They contain a high concentration of specific proteins, nucleic acids, and lipids, reflecting but not identical to the composition of the parent cell. The inherent characteristics and variety of EVs give them extensive and unique advantages in the field of cancer identification and treatment. Recently, EVs have been recognized as potential tumor markers for the detection of cancer. Aptamers, which are molecules of single-stranded DNA or RNA, demonstrate remarkable specificity and affinity for their targets by adopting distinct tertiary structures. Aptamers offer various advantages over their protein counterparts, such as reduced immunogenicity, the ability for convenient large-scale synthesis, and straightforward chemical modification. In this review, we summarized EVs biogenesis, sample collection, isolation, storage and characterization, and finally provided a comprehensive survey of analysis techniques for EVs detection that are based on aptamers.

The Effect of Thrombin-gelatin Matrix Compared With Absorbable Gelatin Sponge on Intraoperative Hemostasis in Unilateral Open-door Laminoplasty: A Randomized Controlled Trial.

STUDY DESIGN: Prospective, randomized, parallel-controlled trial. OBJECTIVE: The primary aim of this study was to determine whether hrombin-gelatin matrix (TGM) combined with an absorbable gelatin sponge (AGS) could more greatly reduce Intraoperative blood loss (IBL) in unilateral open-door laminoplasty than the sole use of an AGS could. The secondary aims were to evaluate the hemostatic efficiency, amount of postoperative bleeding and safety of the application of TGM combined with an AGS. SUMMARY OF BACKGROUND DATA: IBL during cervical laminoplasty is substantial and is a proper indication for the application of hemostatic agents. However, we are unaware of any clinical trials on the application of TGM and an AGS in posterior cervical spine surgery. METHODS: A total of 80 consecutive patients who underwent unilateral open-door laminoplasty, were enrolled from September 2020 to March 2022. Patients were randomized into two groups, the TGM-AGS group and the AGS group, with 40 patients in each group. The primary outcome was IBL. Other outcomes included the duration of operation, duration of hemostasis, duration of drainage, maximum decrease in hemoglobin(Hb), length of hospital stay, volume of drainage, number of drainage days, occurrence of adverse events, coagulation indicators and patient-reported outcome measures (PROMs). RESULTS: The mean IBL for patients in the TGM-AGS group (75.22 mL ±21.83 mL) was significantly lower than that in the AGS group(252.43 mL ±57.39 mL)(mean difference=177.21 mL, 95% confidence interval [CI], 157.88 mL -196.53 mL, t=18.25, P<0.001); the duration of hemostasis, volume of drainage, days of drainage in the TGM group and maximum decrease in Hb were also significantly less than those in the AGS group (P<0.01). CONCLUSION: The hemostatic efficacy of TGM-AGS is better than that of an AGS alone in IBL. TGM-AGS is also superior to an AGS alone in the evaluation of hemostatic efficiency and postoperative bleeding.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Recent Advances in and Application of Fluorescent Microspheres for Multiple Nucleic Acid Detection.

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.

Bacterial abundant taxa exhibit stronger environmental adaption than rare taxa in the Arctic Ocean sediments.

Marine bacteria influence Earth's environmental dynamics in fundamental ways by controlling the biogeochemistry and productivity of the oceans. However, little is known about the survival strategies of their abundant and rare taxa, especially in polar marine environments. Here, bacterial environmental adaptation, community assembly processes, and co-occurrence patterns between abundant and rare taxa were compared in the Arctic Ocean sediments. Results indicated that the diversity of rare taxa is significantly higher than that of abundant taxa, whereas the distance-decay rate of rare taxa community similarity is over 1.5 times higher than that of abundant taxa. Furthermore, abundant taxa exhibited broader environmental breadth and stronger phylogenetic signals compared to rare taxa. Additionally, the community assembly processes of the abundant taxa were predominantly governed by 81% dispersal limitation, while rare taxa were primarily influenced by 48% heterogeneous selection. The co-occurrence network further revealed the abundant taxa formed a more complex network to enhance their environmental adaptability. This study revealed the differences in environmental responses and community assembly processes between bacterial abundant and rare taxa in polar ocean sediments, providing some valuable insights for understanding their environmental adaptation strategies in marine ecosystems.

Distinct strategies of the habitat generalists and specialists in the Arctic sediments: Assembly processes, co-occurrence patterns, and environmental implications.

Microorganisms could be classified as habitat generalists and specialists according to their niche breadth, uncovering their survival strategy is a crucial topic in ecology. Here, differences in environmental adaptation, community assemblies, co-occurrence patterns, and ecological functions between generalists and specialists were explored in the Arctic marine sediments. Compared to specialists, generalists showed lower alpha diversity but stronger environmental adaption, and dispersal limitation contributed more to the community assembly of specialists (74 %) than generalists (46 %). Furthermore, the neutral theory model demonstrated that generalists (m = 0.20) had a higher immigration rate than specialists (m = 0.02), but specialists exhibited more complex co-occurrence patterns than generalists. Our results also found that generalists may play more important roles in C, N, S metabolism but are weaker in carbon fixation and xenobiotic biodegradation and metabolism. This study would broaden our understanding of bacterial generalists' and specialists' survival strategies, and further reveal their ecological functions in marine sediments.

Effects of Cd(II) on nitrogen removal by a heterotrophic nitrification aerobic denitrification bacterium Pseudomonas sp. XF-4.

Simultaneous heterotrophic nitrification and aerobic denitrification (SND) is gaining tremendous attention due to its high efficiency and low cost in water treatment. However, SND on an industrial scale is still immature since effects of coexisting pollutants, for example, heavy metals, on nitrogen removal remains largely unresolved. In this study, a HNAD bacterium (Pseudomonas sp. XF-4) was isolated. It could almost completely remove ammonium and nitrate at pH 5-9 and temperature 20 ℃-35 ℃ within 10 h, and also showed excellently simultaneous nitrification and denitrification efficiency under the coexistence of any two of inorganic nitrogen sources with no intermediate accumulation. XF-4 could rapidly grow again after ammonium vanish when nitrite or nitrate existed. There was no significant effects on nitrification and denitrification when Cd(II) was lower than 10 mg/L, and 95 % of Cd(II) was removed by XF-4. However, electron carrier and electron transport system activity was inhibited, especially at high concentration of Cd(II). Overall, this study reported a novel strain capable of simultaneous nitrification and denitrification coupled with Cd(II) removal efficiently. The results provided new insights into treatment of groundwater or wastewater contaminated by heavy metals and nitrogen.

Acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is a haematological malignancy characterized by the uncontrolled proliferation of immature lymphoid cells. Over past decades, significant progress has been made in understanding the biology of ALL, resulting in remarkable improvements in its diagnosis, treatment and monitoring. Since the advent of chemotherapy, ALL has been the platform to test for innovative approaches applicable to cancer in general. For example, the advent of omics medicine has led to a deeper understanding of the molecular and genetic features that underpin ALL. Innovations in genomic profiling techniques have identified specific genetic alterations and mutations that drive ALL, inspiring new therapies. Targeted agents, such as tyrosine kinase inhibitors and immunotherapies, have shown promising results in subgroups of patients while minimizing adverse effects. Furthermore, the development of chimeric antigen receptor T cell therapy represents a breakthrough in ALL treatment, resulting in remarkable responses and potential long-term remissions. Advances are not limited to treatment modalities alone. Measurable residual disease monitoring and ex vivo drug response profiling screening have provided earlier detection of disease relapse and identification of exceptional responders, enabling clinicians to adjust treatment strategies for individual patients. Decades of supportive and prophylactic care have improved the management of treatment-related complications, enhancing the quality of life for patients with ALL.

The promotion of vascular reconstruction by hierarchical structures in biodegradable small-diameter vascular scaffolds.

Tissue engineering of small-diameter vessels remains challenging due to the inadequate ability to promote endothelialization and infiltration of smooth muscle cells (SMCs). Ideal vascular graft is expected to provide the ability to support endothelial monolayer formation and SMCs infiltration. To achieve this, vascular scaffolds with both orientation and dimension hierarchies were prepared, including hierarchically random vascular scaffold (RVS) and aligned vascular scaffold (AVS), by utilizing degradable poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) and the blend of PCE/gelatin (PCEG) as raw materials. In addition to the orientation hierarchy, dimension hierarchy with small pores in the inner layer and large pores in the outer layer was also constructed in both RVS and AVS to further investigate the promotion of vascular reconstruction by hierarchical structures in vascular scaffolds. The results show that the AVS with an orientation hierarchy that consists with the natural vascular structure had better mechanical properties and promotion effect on the proliferation of vascular cells than RVS, and also exhibited excellent contact guidance effects on cells. While the dimension hierarchy in both RVS and AVS was favorable to the rapid infiltration of SMCs in a short culture time in vitro. Besides, the results of subcutaneous implantation further demonstrate that AVS achieved a fully infiltrated outer layer with wavy elastic fibers-mimic strips formation by day 14, ascribing to hierarchies of aligned orientation and porous dimension. The results further indicate that the scaffolds with both orientation and dimension hierarchical structures have great potential in the application of promoting the vascular reconstruction.

Computer-assisted decision support for the usage of preventive antibacterial therapy in children with febrile pyelonephritis: A preliminary study.

Urinary tract infection (UTI) is one of the most common infectious diseases among children, but there is controversy regarding the use of preventive antibiotics for children first diagnosed with febrile pyelonephritis. To the best of our knowledge, no studies have addressed this issue by the deep learning technology. Therefore, in the current study, we conducted a study using Tc99m-DMSA renal static imaging data to investigate the need for preventive antibiotics on children first diagnosed with febrile pyelonephritis under 2 years old. The self-collected dataset comprised 64 children who did not require preventive antibiotic treatments and 112 children who did. Using several classic deep learning models, we verified that it is feasible to screen whether the first diagnosed children with febrile pyelonephritis require preventive antibacterial therapy, achieving a graded diagnosis. With the AlexNet model, we obtained accuracy of 84.05%, sensitivity of 81.71% and specificity of 86.70%, respectively. The experimental results indicate that deep learning technology could provide a new avenue to implement computer-assisted decision support for the diagnosis of the febrile pyelonephritis.