Alkyl effects on charge recombination in copper electrolyte-based dye-sensitized solar cells: Insights for targeted molecular design towards high performance.

Two quinoxaline dyes utilized in copper-electrolyte-based dye-sensitized solar cells (Cu-DSSCs) are theoretically investigated to analyze the impact of alkyl chains on dye performance. The investigation shows that ZS4, known for its record efficiency of up to 13.2 %, exhibits higher electron coupling and fewer binding sites for dye-[Cu(tmby)2]2+ interaction compared to ZS5. Contrary to common belief, alkyl chains are found to not only provide shielding but also hinder the interaction between dye and [Cu(tmby)2]2+ by influencing the optimal conformation of dyes, thereby impeding the charge recombination process. It is crucial to consider the influence of alkyl chains on dye conformation when discussing the relationship between dye structure and performance, rather than oversimplifying it as often done traditionally. Building on these findings, eight dyes are strategically designed by adjusting the position of the alkyl chain to further decrease charge recombination compared to ZS4. Theoretical evaluation of these dyes reveals that changing the alkyl chain on the nitrogen atom from 2-ethylhexyl (ZS4) to 1-hexylheptyl (D3-2) not only reduces the charge recombination rate but also enhances light harvesting ability. Therefore, D3-2 shows potential as a candidate for experimental synthesis of high-performance Cu-DSSCs with improved efficiency.

Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.

STUDY QUESTION: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles? SUMMARY ANSWER: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO2) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy. WHAT IS KNOWN ALREADY: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods. STUDY DESIGN SIZE DURATION: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study. PARTICIPANTS/MATERIALS SETTING METHODS: Daily average levels of six air pollutants (fine particulate matter (PM2.5), inhalable particulate matter (PM10), SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO2 (33.40%) and NO2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m2 and those under 35 years old. LIMITATIONS REASONS FOR CAUTION: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health. STUDY FUNDING/COMPETING INTERESTS: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Droplet-based single-cell sequencing: Strategies and applications.

Notable advancements in single-cell omics technologies have not only addressed longstanding challenges but also enabled unprecedented studies of cellular heterogeneity with unprecedented resolution and scale. These strides have led to groundbreaking insights into complex biological systems, paving the way for a more profound comprehension of human biology and diseases. The droplet microfluidic technology has become a crucial component in many single-cell sequencing workflows in terms of throughput, cost-effectiveness, and automation. Utilizing a microfluidic chip to encapsulate and profile individual cells within droplets has significantly improved single-cell research. Therefore, this review aims to comprehensively elaborate the droplet microfluidics-assisted omics methods from a single-cell perspective. The strategies for using droplet microfluidics in the realms of genomics, epigenomics, transcriptomics, and proteomics analyses are first introduced. On this basis, the focus then turns to the latest applications of this technology in different sequencing patterns, including mono- and multi-omics. Finally, the challenges and further perspectives of droplet-based single-cell sequencing in both foundational research and commercial applications are discussed.

DCC in the cerebral cortex is required for cognitive functions in mouse.

Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI). Critically, the defective sensorimotor gating could be restored by olanzapine, an antipsychotic drug. Furthermore, we found that the levels of p-AKT and p-GSK3α/ß were decreased, which was responsible for impaired PPI in the DCC-deficient mice. Finally, the DCC-deficient mice also displayed reduced spine density of pyramidal neurons and disturbed delta-oscillations. Our data, for the first time, identified and explored downstream substrates and signaling pathway of DCC which supports the hypothesis that DCC is a SZ-related risky gene and when defective, may promote SZ-like pathogenesis and behavioral phenotypes in mice.

Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis.

BACKGROUND: Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle. RESULTS: Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. The genetically engineered self-assembled particles neoantigen-FNs with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly drainage to and continuously accumulate in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8+ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier. CONCLUSIONS: Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently drainage to lymph nodes and induce efficient antitumor immune responses.

Photo-electrochemical sensor based on BiOI/ZnIn2S4 heterojunction for detecting hydrogen peroxide and dopamine.

Photoelectrochemical (PEC) detection as a potential development strategy for hydrogen peroxide and dopamine sensors has received extensive attentions. Herein, BiOI/ZnIn2S4-X (X = n (BiOI)/n(ZnIn2S4)) heterojunction was synthesized using various molar ratios via a two-step method. A series of characterization techniques were employed to analyze the composition, surface structure, valence state, and optical properties of BiOI/ZnIn2S4-X. The results show that BiOI/ZnIn2S4-X perform significantly better than both BiOI and ZnIn2S4. Furthermore, BiOI/ZnIn2S4-9% exhibits superior visible light absorption capacity and photocurrent response among all of the BiOI/ZnIn2S4-X tested. Therefore, a PEC sensor was developed using BiOI/ZnIn2S4-9% for the detection of hydrogen peroxide and dopamine. The linear detection range for hydrogen peroxide spans from to 1 ~ 40,000 µM, with the LOD of 0.036 µM (S/N = 3). For dopamine, the corresponding values are 2 ~ 250 µM for the linear detection range, and 0.017 µM for the LOD, respectively. The sensor exhibits demonstrates excellent stability, reproducibility and resistance to interference, enabling the detection of real samples and thus holds promising application potential.

Serotonergic transmission plays differentiated roles in the rapid and sustained antidepressant-like effects of ketamine.

BACKGROUND AND PURPOSE: The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5-HT in the antidepressant effects of ketamine remains unclear. EXPERIMENTAL APPROACH: The chronic restraint stress procedure was performed to induce depression-like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant-like effects of ketamine. Tph2 knockout or depletion of 5-HT by PCPA and 5,7-DHT were used to manipulate the brain 5-HT system. ELISA and fibre photometry recordings were used to measure extracellular 5-HT levels in the brain. KEY RESULTS: 60 min after injection, ketamine (10 mg·kg-1, i.p.) produced rapid antidepressant-like effects and increased brain 5-HT levels. After 24 h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5-HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24 h) but not rapid (60 min) antidepressant-like effects of ketamine were abrogated by PCPA and 5,7-DHT, or by Tph2 knockout. Importantly, NBQX (10 mg·kg-1, i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5-HT levels and abolished the sustained antidepressant-like effects of ketamine in naïve or CRS-treated mice. CONCLUSION AND IMPLICATIONS: This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant-like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets.

Haploinsufficiency of intraflagellar transport protein 172 causes autism-like behavioral phenotypes in mice through BDNF.

INTRODUCTION: Primary cilia are hair-like solitary organelles growing on most mammalian cells that play fundamental roles in embryonic patterning and organogenesis. Defective cilia often cause a suite of inherited diseases called ciliopathies with multifaceted manifestations. Intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium, actively facilitates the formation and absorption of primary cilia. IFT172 is the largest component of the IFT-B complex, and its roles in Bardet-Biedl Syndrome (BBS) have been appreciated with unclear mechanisms. OBJECTIVES: We performed a battery of behavioral tests with Ift172 haploinsufficiency (Ift172+/-) and WT littermates. We use RNA sequencing to identify the genes and signaling pathways that are differentially expressed and enriched in the hippocampus of Ift172+/- mice. Using AAV-mediated sparse labeling, electron microscopic examination, patch clamp and local field potential recording, western blot, luciferase reporter assay, chromatin immunoprecipitation, and neuropharmacological approach, we investigated the underlying mechanisms for the aberrant phenotypes presented by Ift172+/- mice. RESULTS: Ift172+/- mice displayed excessive self-grooming, elevated anxiety, and impaired cognition. RNA sequencing revealed enrichment of differentially expressed genes in pathways relevant to axonogenesis and synaptic plasticity, which were further confirmed by less spine density and synaptic number. Ift172+/- mice demonstrated fewer parvalbumin-expressing neurons, decreased inhibitory synaptic transmission, augmented theta oscillation, and sharp-wave ripples in the CA1 region. Moreover, Ift172 haploinsufficiency caused less BDNF production and less activated BDNF-TrkB signaling pathway through transcription factor Gli3. Application of 7,8-Dihydroxyflavone, a potent small molecular TrkB agonist, fully restored BDNF-TrkB signaling activity and abnormal behavioral phenotypes presented by Ift172+/- mice. With luciferase and chip assays, we provided further evidence that Gli3 may physically interact with BDNF promoter I and regulate BDNF expression. CONCLUSIONS: Our data suggest that Ift172 per se drives neurotrophic effects and, when defective, could cause neurodevelopmental disorders reminiscent of autism-like disorders.

Intricate microbe-plant-metabolic remodeling mediated by intercropping enhances the quality of Panax quinquefolius L.

Improving the cultivation mode and technology for traditional Chinese medicine has become important for its sustainable development. Monoculture enhances plant diseases, which decreases yield and quality. Intercropping is an effective measure to counterbalance that negative effect. In this study, we focused on Panax quinquefolium L. (ginseng) and four treatments were set up: the control without intercropping, P. quinquefolius + ryegrass (Lolium perenne L.), P. quinquefolius + red clover (Trifolium pratense L.), and P. quinquefolius + ryegrass + red clover. An LC-MS/MS system was used to detect the changes in the P. quinquefolius secondary metabolites, and high-throughput sequencing technology was used to determine the changes in the P. quinquefolius' rhizosphere soil microorganisms. Ginsenoside content, soil enzyme activities, and arbuscular mycorrhizal infection rate of P. quinquefolius were also measured using HPLC, ELISA kits, and microscopy, respectively. Co-intertia and Pearson's analysis were performed to explore the relationship between the metabolites and the P. quinquefolius microorganisms. Intercropping significantly increased the content of ginsenoside metabolites and recruited a large number of beneficial bacteria to the P. quinquefolius rhizosphere. The P. quinquefolius secondary metabolites were associated with the rhizosphere microbial community. For example, the dominant microorganisms, such as Acidobacteriota and Chloroflexi, played a key role in promoting the synthesis of ginsenoside Rd and (20R) ginsenoside Rg3 by P. quinquefolius. Intercropping led to changes in the P. quinquefolius secondary metabolites by driving and reshaping the rhizosphere microorganisms. These findings revealed the potential application of intercropping for improving the quality of P. quinquefolius.

Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus.

BACKGROUND: Mutations in mitochondrial tRNA (mt-tRNA) genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus (T2DM). We pre-viously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA Trp A5514G and tRNA Ser(AGY) C12237T variants, however, the effects of these mt-tRNA variants on T2DM progression are largely unknown. AIM: To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic, molecular, and biochemical levels. METHODS: Cytoplasmic hybrid (cybrid) cells carrying both m.A5514G and m.C12237T variants, and healthy control cells without these mitochondrial DNA (mtDNA) variants were generated using trans-mitochondrial technology. Mitochondrial features, including mt-tRNA steady-state level, levels of adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mtDNA copy number, nicotinamide adenine dinucleotide (NAD+)/NADH ratio, enzymatic activities of respiratory chain complexes (RCCs), 8-hydroxy-deo-xyguanine (8-OhdG), malondialdehyde (MDA), and superoxide dismutase (SOD) were examined in cell lines with and without these mt-tRNA variants. RESULTS: Compared with control cells, the m.A5514G variant caused an approximately 35% reduction in the steady-state level of mt-tRNA Trp (P < 0.0001); however, the m.C12237T variant did not affect the mt-tRNA Ser(AGY) steady-state level (P = 0.5849). Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells: ATP, MMP, NAD+/NADH ratio, enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells (P < 0.05 for all measures). By contrast, the levels of ROS, 8-OhdG and MDA were significantly increased (P < 0.05 for all measures), but mtDNA copy number was not affected by m.A5514G and m.C12237T variants (P = 0.5942). CONCLUSION: The m.A5514G variant impaired mt-tRNA Trp metabolism, which subsequently caused mitochondrial dysfunction. The m.C12237T variant did not alter the steady-state level of mt-tRNA Ser(AGY), indicating that it may be a modifier of the m.A5514G variant. The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Association between composite dietary antioxidant index and stroke among individuals with diabetes.

BACKGROUND: Recent research has underscored the potentially protective role of dietary antioxidants against chronic conditions, such as cardiovascular diseases and stroke. The composite dietary antioxidant index (CDAI), which reflects the overall intake of key dietary antioxidants, has been identified as a crucial metric for exploring this relationship. Although previous research has shown a negative correlation between CDAI levels and stroke risk in prediabetic individuals, there remains a substantial gap in understanding this association among individuals with dia-betes, who are at an inherently greater risk for cerebrovascular events. AIM: To investigate the association between CDAI and stroke risk in individuals with diabetes. METHODS: Using a cross-sectional study design, this investigation analyzed data from the National Health and Nutrition Examination Survey spanning from 2003 to 2018 that included 6735 participants aged over 20 years with diabetes. The CDAI was calculated from 24-h dietary recalls to assess intake of key antioxidants: Vitamins A, C, and E; carotenoids; selenium; and zinc. Multivariate logistic regression and restricted cubic spline analysis were used to rigorously examine the relationship between CDAI and stroke risk. RESULTS: The participant cohort, with an average age of 59.5 years and a slight male majority, reflected the broader demographic characteristics of individuals with diabetes. The analysis revealed a strong inverse relationship between CDAI levels and stroke risk. Remarkably, those in the highest quintile of CDAI demonstrated a 43% lower prevalence of stroke compared to those in the lowest quintile, even after adjustments for various confounders. This finding not only highlights the negative association between CDAI and stroke risk but also underscores the significant potential of antioxidant-rich diets in reducing stroke prevalence among patients with diabetes. CONCLUSION: Our findings suggested that CDAI was inversely associated with stroke prevalence among patients with diabetes. These results suggest incorporating antioxidant-rich foods into dietary regimens as a potential strategy for stroke prevention.

Bacterial extracellular vesicle: A non-negligible component in biofilm life cycle and challenges in biofilm treatments.

Bacterial biofilms, especially those formed by pathogens, have been increasingly impacting human health. Bacterial extracellular vesicle (bEV), a kind of spherical membranous structure released by bacteria, has not only been reported to be a component of the biofilm matrix but also plays a non-negligible role in the biofilm life cycle. Nevertheless, a comprehensive overview of the bEVs functions in biofilms remains elusive. In this review, we summarize the biogenesis and distinctive features characterizing bEVs, and consolidate the current literature on their functions and proposed mechanisms in the biofilm life cycle. Furthermore, we emphasize the formidable challenges associated with vesicle interference in biofilm treatments. The primary objective of this review is to raise awareness regarding the functions of bEVs in the biofilm life cycle and lay the groundwork for the development of novel therapeutic strategies to control or even eliminate bacterial biofilms.

Radiosynthesis of [18F]brequinar for in vivo PET imaging of hDHODH for potential studies of acute myeloid leukemia and cancers.

Dihydroorotate dehydrogenase (DHODH), an enzyme that plays a critical role in the de novo pyrimidine biosynthesis, has been recognized as a promising target for the treatment of diseases that involve cellular proliferation, such as autoimmune diseases and cancers. Pharmacological inhibition of human DHODH (hDHODH) that offers a potential therapeutic strategy for the treatment in adult subjects with acute myeloid leukemia (AML) has recently been supported by phase I/II clinical trials for the treatment of patients with relapsed/refractory AML. To facilitate the development of optimized hDHODH inhibitors, the presence of an in vivo imaging probe that is able to demonstrate in vivo target engagement is critical and desirable. Brequinar is one of the most potent hDHODH inhibitors so far discovered. In this work, we use a copper-mediated radiofluorination (CMRF) strategy and compare the chemical design and radiosynthesis starting from either pinacole boronate p-nitrobenzyl ester (4) or tributylstannate (tin) p-nitrobenzyl ester (5), chosen for their suitability as a precursor to [18F]brequinar. We report here the design, synthesis, radiolabeling and characterization of [18F]brequinar, and a preliminary PET imaging study of DHODH in vivo. This study provides the strategies to create [18F]brequinar, the first hDHODH inhibitor PET radiotracer, which will facilitate its use as a tool (theranostics) for hDHODH drug development and for diagnosis and monitoring therapeutic efficacy in AML and cancers.

Research on jujube storage and preservation system based on Internet of Things (IoT).

With the surge in Xinjiang jujube production, there has been a concurrent increase in storage losses, posing an ongoing challenge for farmers to preserve the freshness of the jujubes. To tackle this issue, a novel storage and freshness control system for jujubes, integrating Internet of Things technology, has been developed. The control system is centered around a programmable logic controller (PLC) and utilizes an HMI as the interface for human-computer interaction. It is structured with distinct layers, including equipment, transportation, and application layers. By integrating with the Internet of Things cloud platform, data transmission between the device layer and the cloud server is ensured through the use of the TCP/IP protocol over a 4G network. A mobile app enables remote control functionality for monitoring and managing the storage and preservation environment. Experimental results demonstrate the system's stable performance, enabling remote monitoring and convenient operation by management personnel during the jujube storage and preservation process. This contributes to enhancing automation levels in jujube storage, extending its storage cycle while maintaining quality standards, thus providing valuable insights into intelligent fruit and vegetable storage practices in Xinjiang.

The value of combined detection of specific immunoglobulin E, interleukin-6 and regulatory T cells in predicting the risk of postoperative recurrence in patients with eosinophilic chronic rhinosinusitis and nasal polyps.

Background: To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic Chronic rhinosinusitis with nasal polyps (EcRswNP). Methods: A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and nonrecurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. Results: The proportion of asthma patients, nasal congestion VAS score, and peripheral blood Eos% content in the RG exceeded that in the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL6 in the RG were higher than those in the NRG, while the level of peripheral blood Treg was lower than that in the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). Conclusions: The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.

Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.

BACKGROUND: Uterine endometrial cancer (UEC) is a common gynecological estrogen-dependent carcinoma, usually accompanied by intermenstrual bleeding. Active heme metabolism frequently plays an increasingly important role in many diseases, especially in cancers. Tumor-associated macrophages (TAMs) are the major population in the immune microenvironment of UEC. However, the roles of heme metabolisms in the crosstalk between UEC cells (UECCs) and macrophages are unclear. MATERIALS AND METHODS: In our study, by using TCGA database analysis, integration analysis of the protein-protein interaction (PPI) network and sample RNA transcriptome sequencing were done. The expression level of both heme-associated molecules and iron metabolism-related molecules were measured by quantitative real-time polymerase chain reaction. Heme level detection was done through dehydrohorseradish peroxidase assay. In addition to immunohistochemistry, phagocytosis assay of macrophages, immunofluorescence staining, intracellular ferrous iron staining, as well as enzyme-linked immune sorbent assay were performed. RESULTS: In the study, we verified that heme accumulation in UECCs is apparently higher than in endometrial epithelium cells. Low expression of succinate dehydrogenase B under the regulation of estrogen contributes to over-production of succinate and heme accumulation in UECC. More importantly, excessive heme in UECCs impaired macrophage phagocytosis by regulation of CD36. Mechanistically, this process is dependent on toll-like receptor (TLR4)/type I interferons alpha (IFN Iα) regulatory axis in macrophage. CONCLUSION: Collectively, these findings elucidate that active heme metabolism of UECCs directly decreases phagocytosis by controlling the secretion of TLR4-mediated IFN Iα and the expression of CD36, and further contributing to the immune escape of UEC.

Association between glucose levels of children with type 1 diabetes and parental economic status in mobile health application.

BACKGROUND: The glycemic control of children with type 1 diabetes (T1D) may be influenced by the economic status of their parents. AIM: To investigate the association between parental economic status and blood glucose levels of children with T1D using a mobile health application. METHODS: Data from children with T1D in China's largest T1D online community, Tang-TangQuan®. Blood glucose levels were uploaded every three months and parental economic status was evaluated based on annual household income. Children were divided into three groups: Low-income (< 30000 Yuan), middle-income (30000-100000 Yuan), and high-income (> 100000 yuan) (1 Yuan = 0.145 United States Dollar approximately). Blood glucose levels were compared among the groups and associations were explored using Spearman's correlation analysis and multivariable logistic regression. RESULTS: From September 2015 to August 2022, 1406 eligible children with T1D were included (779 female, 55.4%). Median age was 8.1 years (Q1-Q3: 4.6-11.6) and duration of T1D was 0.06 years (0.02-0.44). Participants were divided into three groups: Low-income (n = 320), middle-income (n = 724), and high-income (n = 362). Baseline hemoglobin A1c (HbA1c) levels were comparable among the three groups (P = 0.072). However, at month 36, the low-income group had the highest HbA1c levels (P = 0.036). Within three years after registration, glucose levels increased significantly in the low-income group but not in the middle-income and high-income groups. Parental economic status was negatively correlated with pre-dinner glucose (r = -0.272, P = 0.012). After adjustment for confounders, parental economic status remained a significant factor related to pre-dinner glucose levels (odds ratio = 13.02, 95%CI: 1.99 to 126.05, P = 0.002). CONCLUSION: The blood glucose levels of children with T1D were negatively associated with parental economic status. It is suggested that parental economic status should be taken into consideration in the management of T1D for children.

AI support for colonoscopy quality control using CNN and transformer architectures.

BACKGROUND: Construct deep learning models for colonoscopy quality control using different architectures and explore their decision-making mechanisms. METHODS: A total of 4,189 colonoscopy images were collected from two medical centers, covering different levels of bowel cleanliness, the presence of polyps, and the cecum. Using these data, eight pre-trained models based on CNN and Transformer architectures underwent transfer learning and fine-tuning. The models' performance was evaluated using metrics such as AUC, Precision, and F1 score. Perceptual hash functions were employed to detect image changes, enabling real-time monitoring of colonoscopy withdrawal speed. Model interpretability was analyzed using techniques such as Grad-CAM and SHAP. Finally, the best-performing model was converted to ONNX format and deployed on device terminals. RESULTS: The EfficientNetB2 model outperformed other architectures on the validation set, achieving an accuracy of 0.992. It surpassed models based on other CNN and Transformer architectures. The model's precision, recall, and F1 score were 0.991, 0.989, and 0.990, respectively. On the test set, the EfficientNetB2 model achieved an average AUC of 0.996, with a precision of 0.948 and a recall of 0.952. Interpretability analysis showed the specific image regions the model used for decision-making. The model was converted to ONNX format and deployed on device terminals, achieving an average inference speed of over 60 frames per second. CONCLUSIONS: The AI-assisted quality system, based on the EfficientNetB2 model, integrates four key quality control indicators for colonoscopy. This integration enables medical institutions to comprehensively manage and enhance these indicators using a single model, showcasing promising potential for clinical applications.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Obesity-Related Ciliopathies: Focus on Advances of Biomarkers.

Obesity-related ciliopathies, as a group of ciliopathies including Alström Syndrome and Bardet-Biedl Syndrome, exhibit distinct genetic and phenotypic variability. The understanding of these diseases is highly significant for understanding the functions of primary cilia in the human body, particularly regarding the relationship between obesity and primary cilia. The diagnosis of these diseases primarily relies on clinical presentation and genetic testing. However, there is a significant lack of research on biomarkers to elucidate the variability in clinical manifestations, disease progression, prognosis, and treatment responses. Through an extensive literature review, the paper focuses on obesity-related ciliopathies, reviewing the advancements in the field and highlighting the potential roles of biomarkers in the clinical presentation, diagnosis, and prognosis of these diseases.