Subminimum Inhibitory Concentrations Tetracycline Antibiotics Induce Biofilm Formation in Minocycline-Resistant Klebsiella pneumonia by Affecting Bacterial Physical and Chemical Properties and Associated Genes Expression.

Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.

Biomechanical changes in lower extremity in individuals with knee osteoarthritis in the past decade: A scoping review.

Biomechanic studies can provide a powerful theoretical and scientific basis for studies on knee osteoarthritis (OA), which is of great significance for clinical management as it provides new concepts and methods in clinical and research settings. This study aimed to discuss and summarize biomechanical research on lower extremities in individuals with knee OA in the past ten years. The methodology of this review followed the framework outlined in the Joanna Briggs Institute (JBI) guidelines and strictly followed the checklist for drafting the findings. A literature search was conducted using PubMed, Scopus, Cochrane Library, Embase, Web of Science, Grey literature search in Open Library, and Google Academic databases. Relevant literature was searched from 2011 to 2023. Sixteen studies were included in this scoping review. Biomechanical research on knee OA in the last decade demonstrates that the biomechanics of the hip, knee, and ankle have a profound influence on the pathogenesis and treatment of knee OA. Individuals with knee OA have biomechanical changes in hip, knee, and ankle joints such as a significant defect in the strength of ankle varus muscles, weakness of hip abductor muscle, walking with toes outwards, increased knee adduction moment and angle, and decreased knee extensor moment. As the severity of knee OA increases, the tendency of hip abduction positions also increases. Further research with a longitudinal study design should focus on the determination of the relative importance of different biomechanical and neuromuscular factors in the development and progression of the disease.

Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression.

Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.

Pyriproxyfen enhances germline stem cell proliferation and reduces reproduction in Drosophila by up-regulating juvenile hormone signaling.

BACKGROUND: Pyriproxyfen is an insect growth regulator (IGR) that is effective against various types of insect pests. However, the molecular mechanism underlying pyriproxyfen effects on insect reproduction remains unclear. Thus, in this study, we attempted to uncover the mechanisms underlying the impact of pyriproxyfen on the reproductive system of the model organism Drosophila melanogaster. RESULTS: A significant decrease in Drosophila reproduction was observed after pyriproxyfen treatment. The juvenile hormone (JH) titer was significantly increased (120.4%) in the ovary samples of pyriproxyfen-treated flies. Likewise, the concentrations of key enzymes and the expression of key genes related to the JH signaling pathway were also increased in the pyriproxyfen-treated group compared with the control group. Furthermore, pyriproxyfen treatment significantly increased (15.6%) the number of germline stem cells (GSCs) and significantly decreased (17%) the number of cystoblasts (CBs). However, no significant differences were observed in the number of somatic cells. We performed RNA interference (RNAi) on five key genes (Met, Tai, gce, ftz-f1, and hairy) related to the JH signaling pathway in germ cells using the germ cell-specific Gal4 driver. Interestingly, RNAi of the selected genes significantly decreased the number of both GSCs and CBs in pyriproxyfen-treated transgenic flies. These results further validate that pyriproxyfen enhances GSC proliferation by up-regulating JH signaling. CONCLUSION: Our results indicate that pyriproxyfen significantly decreases reproduction by affecting germ cells in female adult ovaries. The effect of pyriproxyfen on germ cell proliferation and differentiation is mediated by an increase in JH signaling. This study has significant implications for optimizing pest control strategies, developing sustainable agriculture practices, and understanding the mechanism of insecticide action. © 2024 Society of Chemical Industry.

Holistic preconception care: Providing real-time guidance via a mobile app to optimise maternal and child health.

Introduction: Preconception is a critical period to optimise gamete function and early placental development, essential for successful conception and long-term maternal-child health. However, there is a lack of preconception services and consequently, global fertility rates continue to fall and mothers embark on their pregnancy journey in poor health. There is an urgent need to implement a holistic community-level preconception care programme to optimise risk factors for poor fecundability and improve long-term maternal-child health. Method: We reviewed current evidence on fecundability lifestyle risk factors, the efficacy of existing preconception interventions and the use of digital platforms for health optimisation, to create a new digital-based preconception intervention model that will be implemented via an app. We present the theory, content and mode of delivery of this holistic model targeting couples planning for pregnancy. Results: We propose a new model featuring a user-friendly mobile app, which enables couples to self-assess fecundability risks through a personalised risk score that drives a tailored management plan. This tiered management provides anticipatory guidance supported by evidence-based recommen-dations, and promotes ongoing engagement for behavioural optimisation and specialist referrals as required. Based on the health belief model, this new model delivered with a mobile app seeks to shift couples' perceptions about their susceptibility and severity of subfertility, benefits of making a change and barriers to change. Conclusion: Our proposed digital-based intervention model via a mobile app stands to enhance preconcep-tion care by providing personalised risk assessments, real-time feedback and tiered management to optimise preconception reproductive health of couples. This model forms a reference content framework for future preconception care intervention delivery.

Modified spatial architecture of regulatory T cells after neoadjuvant chemotherapy in non-small cell lung cancer patients.

It is crucial to decipher the modulation of regulatory T cells (Tregs) in tumor microenvironment (TME) induced by chemotherapy, which may contribute to improving the efficacy of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer (NSCLC). We retrospectively collected specimens from patients with II-III NSCLC, constituting two cohorts: a neoadjuvant chemotherapy (NAC) cohort (N = 141) with biopsy (N = 58) and postoperative specimens (N = 141), and a surgery-only cohort (N = 122) as the control group. Then, the cell density (Dens), infiltration score (InS), and Treg-cell proximity score (TrPS) were conducted using a panel of multiplex fluorescence staining (Foxp3, CD4, CD8, CK, CD31, ɑSMA). Subsequently, the association of Tregs with cancer microvessels (CMVs) and cancer-associated fibroblasts (CAFs) was analyzed. Patients with NAC treatment have a higher density of Tregs in both paired (P < 0.001) and unpaired analysis (P = 0.022). Additionally, patients with NAC treatment showed higher infiltration score (paired, P < 0.001; unpaired, P = 0.014) and more CD8+T cells around Tregs (paired/unpaired, both P < 0.001). Subgroup analysis indicated that tumors with a diameter of ≤ 5 cm exhibited increase in both Dens(Treg) and InS(Treg), and gemcitabine, pemetrexed and taxel enhanced Dens(Treg) and TrPS(CD8) following NAC. Multivariate analysis identified that the Dens(Tregs), InS(Tregs) and TrPS(CD8) were significantly associated with better chemotherapy response [OR = 8.54, 95%CI (1.69, 43.14), P = 0.009; OR = 7.14, 95%CI (1.70, 30.08), P = 0.024; OR = 5.50, 95%CI (1.09, 27.75), P = 0.039, respectively] and positive recurrence-free survival [HR = 3.23, 95%CI (1.47, 7.10), P = 0.004; HR = 2.70; 95%CI (1.27, 5.72); P = 0.010; HR = 2.55, 95%CI (1.21, 5.39), P = 0.014, respectively]. Moreover, TrPS(CD8) and TrPS(CD4) were negatively correlated with the CMVs and CAFs. These discoveries have deepened our comprehension of the immune-modulating impact of chemotherapy and underscored that the modified spatial landscape of Tregs after chemotherapy should be taken into account for personalized immunotherapy, aiming to ultimately improve clinical outcomes in patients with NSCLC.

Dysfunction of CD8+ T cells around tumor cells leads to occult lymph node metastasis in NSCLC patients.

Occult lymph node metastasis (OLNM) is one of the main causes of regional recurrence in inoperable N0 non-small cell lung cancer (NSCLC) patients following stereotactic ablation body radiotherapy (SABR) treatment. The integration of immunotherapy and SABR (I-SABR) has shown preliminary efficiency in mitigating this recurrence. Therefore, it is necessary to explore the functional dynamics of critical immune effectors, particularly CD8+ T cells in the development of OLNM. In this study, tissue microarrays (TMAs) and multiplex immunofluorescence (mIF) were used to identify CD8+ T cells and functional subsets (cytotoxic CD8+ T cells/predysfunctional CD8+ T cells (CD8+ Tpredys)/dysfunctional CD8+ T cells (CD8+ Tdys)/other CD8+ T cells) among the no lymph node metastasis, OLNM, and clinically evident lymph node metastasis (CLNM) groups. As the degree of lymph node metastasis escalated, the density of total CD8+ T cells and CD8+ Tdys cells, as well as their proximity to tumor cells, increased progressively and remarkably in the invasive margin (IM). In the tumor center (TC), both the density and proximity of CD8+ Tpredys cells to tumor cells notably decreased in the OLNM group compared with the group without metastasis. Furthermore, positive correlations were found between the dysfunction of CD8+ T cells and HIF-1α+CD8 and cancer microvessels (CMVs). In conclusion, the deterioration in CD8+ T cell function and interactive dynamics between CD8+ T cells and tumor cells play a vital role in the development of OLNM in NSCLC. Strategies aimed at improving hypoxia or targeting CMVs could potentially enhance the efficacy of I-SABR.

Computational study of K vacancy with an H interstitial defect in KH2PO4 crystal.

The electronic structures, defect formations, defect transition levels and optical properties for VK+Hi defect models in KDP crystals have been studied based on DFT. Lattice dynamics methods give the most reasonable compensation mechanism for VK, namely compensation with the third-nearest Hi neighbor from VK for the paraelectric (PE) phase and compensation with the fourth-nearest neighbor Hi from VK for the ferroelectric (FE) phase. The defect formation energies indicate that the [Formula: see text] (The superscript represents the charged state, the 'x' represents neutral, ''' represents -1 charge state and '.' represents +1 charge state.) is the main defect type in this kind of defect cluster and a self-trapped electron is located at Hi in the (VK + Hi)' system. For [Formula: see text] system, one electron is accommodated in VK. There is not a new defect state in the band gap. The Hi bonds with the O ion (0.99 Å) form a hydroxyl. For (VK + Hi)' system, the hydroxyl is broken, the Hi exists in an atomic form and introduces new defect states in the band gap. As the large relaxation energy leads to a large Huang-Rhys factor, the Stokes red shifts will significantly affect the optical properties. A broad ultraviolet (UV) absorption band and emission band range from UV to visible are obtained originating from the defect cluster. We believe that the far-violet absorption peaks (167 nm and 179 nm) caused by defect cluster VK+Hi can significantly impact the optical damage threshold of the KDP.

Acinetobacter baumannii biofilm was inhibited by tryptanthrin through disrupting its different stages and genes expression.

Biofilm formation plays a significant role in antibiotic resistance, necessitating the search for alternative therapies against biofilm-associated infections. This study demonstrates that 20 µg/mL tryptanthrin can hinder biofilm formation above 50% in various A. baumannii strains. Tryptanthrin impacts various stages of biofilm formation, including the inhibition of surface motility and eDNA release in A. baumannii, as well as an increase in its sensitivity to H202. RT-qPCR analysis reveals that tryptanthrin significantly decreases the expression of the following genes: abaI (19.07%), abaR (33.47%), bfmR (43.41%), csuA/B (64.16%), csuE (50.20%), ompA (67.93%), and katE (72.53%), which are related to biofilm formation and quorum sensing. Furthermore, tryptanthrin is relatively safe and can reduce the virulence of A. baumannii in a Galleria mellonella infection model. Overall, our study demonstrates the potential of tryptanthrin in controlling biofilm formation and virulence of A. baumannii by disrupting different stages of biofilm formation and intercellular signaling communication.

Efficacy of levetiracetam combined with oxcarbazepine in the treatment of adults with temporal lobe epilepsy and its impact on memory and cognitive function.

OBJECTIVE: To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy. METHODS: This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed. RESULTS: CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy. CONCLUSION: Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.

Interfacial modulation of hollow ZnS-SnS2 microboxs by Ti3C2Tx MXene to construct three-dimensional hybrid anodes for lithium-ion batteries with ultra high stability at low temperature.

Metal sulfides exhibit obvious volume expansion due to the inherent poor conductivity and large temperature fluctuations, leading to reduced storage capacity. Herein, an electrostatic self-assembly strategy was proposed to fabricate a three-dimensional (3D) polyaniline (PANI) encapsulated hollow ZnS-SnS2 (H-ZSS) heterojunction confined on Ti3C2Tx MXene nanosheets (H-ZnS-SnS2@MXene@PANI, denoted as H-ZSSMP), which exhibits remarkable reversible capacity and cyclic stability (520.3 mAh/g at 2 A/g after 1000 cycles) at room temperature. Additionally, specific capacity can stabilized at 362.5 mAh/g for 250 cycles at -20 °C. A full cell with the configuration of H-ZSSMP//lithium iron phosphate (LiFePO4) can retain a satisfactory reversible capacity of 424.7 mAh/g after 100 cycles at 0.1 C. Theory calculations confirm heterogeneous interface can accelerate the transfer of ions through the interfacial regulation effect of MXene on H-ZSS. Our work provides a simple strategy to improve the capacity and stability of lithium-ion batteries (LIBs), as well as the new applications of MXene and bimetallic sulfides as anode materials, which will facilitate the development of MXene based composites for energy storage.

RGIE: A Gene Selection Method Related to Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant tumor with a high degree of malignancy, invasiveness, and metastasis rate. Radiotherapy, as an important adjuvant therapy for HNSCC, can reduce the postoperative recurrence rate and improve the survival rate. Identifying the genes related to HNSCC radiotherapy resistance (HNSCC-RR) is helpful in the search for potential therapeutic targets. However, identifying radiotherapy resistance-related genes from tens of thousands of genes is a challenging task. While interactions between genes are important for elucidating complex biological processes, the large number of genes makes the computation of gene interactions infeasible. METHODS: We propose a gene selection algorithm, RGIE, which is based on ReliefF, Gene Network Inference with Ensemble of Trees (GENIE3) and Feature Elimination. ReliefF was used to select a feature subset that is discriminative for HNSCC-RR, GENIE3 constructed a gene regulatory network based on this subset to analyze the regulatory relationship among genes, and feature elimination was used to remove redundant and noisy features. RESULTS: Nine genes (SPAG1, FIGN, NUBPL, CHMP5, TCF7L2, COQ10B, BSDC1, ZFPM1, GRPEL1) were identified and used to identify HNSCC-RR, which achieved performances of 0.9730, 0.9679, 0.9767, and 0.9885 in terms of accuracy, precision, recall, and AUC, respectively. Finally, qRT-PCR validated the differential expression of the nine signature genes in cell lines (SCC9, SCC9-RR). CONCLUSION: RGIE is effective in screening genes related to HNSCC-RR. This approach may help guide clinical treatment modalities for patients and develop potential treatments.

Reliability, validity, and responsiveness of the simplified Chinese version of the knee injury and Osteoarthritis Outcome Score in patients after total knee arthroplasty.

Objectives: The Knee Injury and Osteoarthritis Outcome Score (KOOS) has been utilized to evaluate short- and long-term outcomes in individuals following knee injuries, such as those with anterior cruciate ligament reconstruction and knee osteoarthritis, but has not yet been applied to individuals undergoing total knee arthroplasty (TKA) in China. The aim of this study was to assess the psychometric properties of the Simplified Chinese version of the KOOS in Chinese individuals undergoing TKA. Methods: This study distributed 170 questionnaires, and assessed the KOOS of the participants, along with requiring them to complete the Short Form 36 (SF-36) survey. There were 35 participants completed a test-retest reliability survey with a 24-h interval, 129 participants completed a pre - surgery survey, and 119 individuals completed a post - surgery survey 6 weeks after the surgery. The following tests were conducted: Cronbach's alpha (α) to assess internal consistency, intraclass correlation coefficient (ICC) to evaluate test-retest reliability, Spearman's correlation coefficient (ρ) to examine construct validity, effect size (ES) to detect measure responsiveness, minimal detectable change (MDC) to assess measurement errors. Floor and ceiling effects (<15%) were also asses evaluated. Results: The simplified Chinese version of the KOOS showed good test-retest reliability in participants after TKA, with an ICC of 0.82-0.97 (95% CI). The internal consistency of the five subscales of the KOOS was good (Cronbach's α = 0.70-0.96). No floor or ceiling effects were found. Regarding construct validity, a strong positive correlation was found between each of the three KOOS subscales (activities of daily living, knee-related Quality of Life, and sport and recreation subscales) and the general health and bodily pain subscales of the SF-36 (0.53 < ρ < 0.61). The subscales of the simplified Chinese version of the KOOS showed responsiveness (ES: 0.68 to 0.86) before and after 6 weeks of physical treatment. The MDC ranged from 10.28 to 23.24. Conclusions: The Chinese version of the KOOS showed good psychometric properties and was found to be valid, reliable, and simple as an assessment tool for symptoms, pain, activity of daily living, sports and recreational activity and quality of life for the Chinese population suffering from TKA.

The prevalence of intimate partner violence and risk factors for women and men in China during the Shanghai 2022 lockdown.

AIMS: Intimate partner violence (IPV) is a global public health concern with negative effects on individuals and families. The present study investigated the prevalence, risk factors and gender disparities associated with IPV during the Shanghai 2022 Covid-19 lockdown - a public health emergency which may have exacerbated IPV. METHODS: We estimated the total IPV prevalence and prevalence of physical, sexual and verbal IPV by using an adapted version of the Extended-Hurt, Insult, Threaten, Scream scale. This cross-sectional study was carried out using a population quota-based sampling of Shanghai residents across 16 districts during the 2022 Shanghai lockdown (N = 2026; 1058 men and 968 women). RESULTS: We found a distinct gendered dynamic, where women reported a significantly higher prevalence of experienced IPV (27.1%, 95% confidence interval [CI]: 23.1-31.4) compared to men (19.8%, 95% CI: 16.1-24.0). Notably, the prevalence estimate mirrored the national lifetime IPV prevalence for women but was over twice as high for men. In multivariable logistic regression analyses, economic stress (income loss: adjusted OR [aOR] = 2.42, 95% CI: 1.28-4.56; job loss: aOR = 1.73, 95% CI: 1.02-2.92; financial worry much more than usual: aOR = 1.89, 95% CI: 1.00-3.57) and household burden (one child at home: aOR = 1.81, 95% CI: 1.12-2.92; not enough food: aOR = 1.67, 95% CI: 1.04-2.70) were associated with increased odds of overall IPV victimization among women but not men. With regard to more serious forms of IPV, job loss (aOR = 2.27, 95% CI: 1.09-4.69) and household burden (two or more children at home: aOR = 2.95, 95% CI: 1.33-7.69) were associated with increased odds of physical IPV against men. For women, a lack of household supplies was associated with increased odds of physical IPV (water: aOR = 3.33, 95% CI: 1.79-6.25; daily supplies: aOR = 2.27, 95% CI: 1.18-4.35). Lack of daily supplies (aOR = 2.17, 95% CI: 1.03-4.55) and job loss (aOR = 2.66, 95% CI: 1.16-6.12) were also associated with increased odds of sexual IPV. CONCLUSIONS: Although a larger proportion of women reported IPV, men experienced greater IPV during the lockdown than previously estimated before the pandemic. Economic stressors, including job loss, and household burden were critical risk factors for serious forms of IPV. Improving gender equality that my account for disparities in IPV in China is critically needed. Policies that mitigate the impact of economic losses during crises can potentially reduce IPV.

Spatiotemporal distribution, interactions and toxic effect of microorganisms and ARGs/MGEs from the bioreaction tank in hospital sewage treatment facility.

Antibiotic resistance genes (ARGs) can be emitted from wastewater to ambient air and impose unignorable inhalable hazards, which could be exacerbated in antibiotic-concentrated hospital sewage. However, whether the ARG-carrying pathogens are more likely to infect cells remains largely unknown. Here, this study investigated and analyzed the spatiotemporal distribution, interaction, and toxicity of airborne microorganisms and their hosting ARGs in a hospital sewage treatment facility. The average concentration of ARGs/MGEs in sewage of bioreaction tank (BRT-W) was 2.27 × 104 gene copies/L. In the air of bioreaction tank (BRT-A), the average concentration of ARGs/MGEs was 15.86 gene copies/m3. In the four seasons, the ARGs concentration of sewage gradually decreased over time; The concentration of ARGs in the air first decreased and then increased. In spring, the concentration of ARGs/MGEs (qacedelta1-01) in BRT-W was highest (1.05 × 105 gene copies/L); The concentration of ARGs/MGEs (strB) in BRT-A in winter was higher than other seasons (26.18 gene copies/m3). Different from the past, this study also paid attention to the pathogenic potential of ARGs/MGEs in the air. The results of cell experiments showed that the cytotoxicity of drug-resistant Escherichia coli could reach Grade V. This suggested that the longer the drug-resistant E. coli were exposed to cells, the greater the cytotoxicity. Moreover, the cytotoxicity of bacteria increased with the increase in exposure time. In spring, the toxic effect of ARGs/MGEs in sewage of BRT-W was highest. Traceability analysis proved that BRT-W was an essential source of microorganisms and ARGs/MGEs in BRT-A. Furthermore, the combined risk of people exposed to the air of BRT in spring was higher than that in other seasons.

Identification of lineage-specific epigenetic regulators FOXA1 and GRHL2 through chromatin accessibility profiling in breast cancer cell lines.

Breast cancer is a heterogeneous disease, and breast cancer cell lines are invaluable for studying this heterogeneity. However, the epigenetic diversity across these cell lines remains poorly understood. In this study, we performed genome-wide chromatin accessibility analysis on 23 breast cancer cell lines, including 2 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-), 3 ER+/HER2+, 3 HER2+, and 15 triple-negative breast cancer (TNBC) lines. These cell lines were classified into three groups based on their chromatin accessibility: the receptor-positive group (Group-P), TNBC basal group (Group-B), and TNBC mesenchymal group (Group-M). Motif enrichment analysis revealed that only Group-P exhibited coenrichment of forkhead box A1 (FOXA1) and grainyhead-like 2 (GRHL2) motifs, whereas Group-B was characterized by the presence of the GRHL2 motif without FOXA1. Notably, Group-M did not show enrichment of either FOXA1 or GRHL2 motifs. Furthermore, gene ontology analysis suggested that group-specific accessible regions were associated with their unique lineage characteristics. To investigate the epigenetic landscape regulatory roles of FOXA1 and GRHL2, we performed knockdown experiments targeting FOXA1 and GRHL2, followed by assay for transposase-accessible chromatin sequencing analysis. The findings revealed that FOXA1 maintains Group-P-specific regions while suppressing Group-B-specific regions in Group-P cells. In contrast, GRHL2 preserves commonly accessible regions shared between Group-P and Group-B in Group-B cells, suggesting that FOXA1 and GRHL2 play a pivotal role in preserving distinct chromatin accessibility patterns for each group. Specifically, FOXA1 distinguishes between receptor-positive and TNBC cell lines, whereas GRHL2 distinguishes between basal-like and mesenchymal subtypes in TNBC lines.

Prenatal diagnosis of ROR-2 related Robinow syndrome presenting with fetal ultrasound findings of mesomelia, vertebral, digital and genital abnormalities.

Autosomal recessive ROR2-Robinow syndrome is caused by pathogenic variants in the ROR2 gene. Fetal ultrasound done on our patient at 24 + 3/7 weeks gestation showed macrocephaly, brachycephaly, flat face, prominent forehead, mild frontal bossing, lower thoracic hemivertebrae, digital abnormalities and micropenis. Fetal trio whole exome sequencing done on amniocytes showed two pathogenic compound heterozygous variants in the ROR2 gene, c.1324 C > T; p.(Arg442*) maternally inherited and c.1366dup; p.(Leu456Profs*3) apparently de novo. c.1324 C > T; p.(Arg442*) is a nonsense variant resulting in protein truncation reported to be associated with RRS3. c.1366dup; p.(Leu456Profs*3) is a frameshift variant predicted to result in protein truncation reported to segregate with the disease in multiple affected individuals from a single large family with distal symphalangism of the fourth finger. Fetal autopsy following pregnancy termination showed a large head with low-set ears, facial abnormalities, mesomelic bone shortening, hemivertebra, fused S3 and S4 vertebral bodies, several fused rib heads and short penis with buried shaft.

Change characteristics, bacteria host, and spread risks of bioaerosol ARGs/MGEs from different stages in sewage and sludge treatment process.

The spread of antibiotic resistance genes (ARGs) in the atmospheric environment has seriously threatened human health. Wastewater treatment plants (WWTPs) are an important source of aerosol ARGs. A large WWTP, including sewage treatment process (SWP) and sludge treatment process (SDP), was selected in North China for sampling in this study. The content of ARGs, mobile genetic elements (MGEs), and bacterial genera in sewage/sludge and aerosols from different process stages was detected. The possible correlation between ARGs/ MGEs and bacteria was analyzed. The risk of antibiotic-resistant bacteria was evaluated and the diffusion of ARGs/MGEs was simulated. The results showed that the concentration of ARGs/MGEs varied as the process progressed, and which in the aeration tank was relatively high. The ARGs/MGEs content in SWP aerosol (8.35-163.27 copies/m3) was higher than that in SDP (5.52-16.36 copies/m3). The main ARGs/MGEs detected in SWP aerosol were tnpA-05, tnpA-04, and ermF, while the main ARGs/MGEs detected in SDP aerosol were sul1, ermF, and blaPAO. ARGs were positively correlated with most bacteria and Escherichia coli with ARGs carries higher cytotoxicity. ARGs/MGEs mainly diffused towards the southeast, which may cause harm to urban residents with the diffusion of aerosols. This study provides clues and theoretical basis for preventing the hazards of ARGs from WWTP sources.

Airborne ARGs/MGEs from two sewage types during the COVID-21: Population, microbe interactions, cytotoxicity, formation mechanism, and dispersion.

During the COVID-2021 epidemic, a large number of antibiotics were used for clinical treatment in hospitals or daily prevention. Sewage from hospital sewage treatment centers (HSTC) and wastewater treatment plants (WWTP) produced a lot of antibiotic-resistance genes/mobile genetic elements (ARGs/MGEs). In this study, the sewage and bioaerosol in the biochemical tank (BT) of an HSTC and a WWTP were sampled throughout the year. The results showed that the average absolute abundance of sewage in BT of WWTP (BTW-W) was higher than sewage in BT of HSTC (BTW-H). Sewage was an important source of microorganisms and ARGs/MGEs in the air of BT. Microorganisms and MGEs were the factors affecting the differences in ARGs/MGEs. Cytotoxicity experiment proved that the cytotoxicity changed from Grade III to Grade IV with the increase in drug-resistant Escherichia coli concentration. According to the formation mechanism formula, the average generation rate of ARGs/MGEs in BT of HSTC was lower than that in WWTP. The diffusion range of ARGs/MGEs of HSTC was larger than that of WWTP. According to the above results, this study found that when people were far away from BT, the health risk of HSTC caused by the diffusion of bioaerosol was higher than WWTP; When people were close to BT, the health risk of WWTP was higher than HSTC due to the aeration of BT. This study provided a basis for public protection of ARGs. In the future, the elimination of airborne ARGs and crowd protection can be further studied in detail.

Change of indocyanine green clearance ability and liver function after transcatheter intra-arterial therapies and its impact on outcomes of resectable hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Indocyanine green (ICG) clearance test is a classical measurement of hepatic reserve, which involves surgical safety and patient recovery of hepatocellular carcinoma (HCC). The authors aim to compare effects of hepatic arterial infusion chemotherapy (HAIC) and transcatheter arterial chemoembolization (TACE) on liver function and outcomes of subsequent hepatectomy. MATERIAL AND METHODS: HCC patients receiving HAIC/TACE in SYSUCC with repeated ICG clearance tests were retrospectively enrolled. ICG eliminating rate (ICG-K), ICG retention rate at 15 min (ICG-R15) and ordinary laboratory tests were collected. Peri-therapeutic changes of values were compared between the groups. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) were employed to validate findings. Post-hepatectomy liver failure (PHLF), overall survival (OS) and recurrence-free survival (RFS) were analyzed in patients with subsequent curative hepatectomy. RESULTS: Two hundred and four patients treated with HAIC ( n =130) and TACE ( n =74) were included. ΔICG-R15 was greater in the HAIC arm before matching (mean, 3.8% vs. 0.7%, P <0.001), after PSM (mean, 4.7% vs. 1.1%, P =0.014) and IPTW (mean, 2.0% vs. -3.6%, P <0.001). No difference was found for ΔALB, ΔALBI, ΔTBIL, ΔALT, ΔAST and ΔPT-INR. Multivariable analyses revealed elder age, cirrhosis, HAIC, greater ΔTBIL and ΔALBI were associated with deteriorating ICG-R15. Among those (105 for HAIC and 48 for TACE) receiving hepatectomy, occurrence of grade B/C PHLF (4.8% vs. 8.3%, P =0.616), OS (median, unreached vs. unreached, P =0.94) and RFS (median, 26.7 vs. 17.1 months, P =0.096) were comparable between the two arms. In subgroup analyses, preoperative HAIC yield superior RFS (median, 26.7 vs. 16.2 months, P =0.042) in patients with baseline ICG-R15 less than or equal to 10%. CONCLUSION: Preoperative FOLFOX-HAIC caused apparent impairment of ICG clearance ability than TACE yet comparable impact on liver function and post-hepatectomy outcomes.