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Abstract Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and posttreatment-specimens from the primary tumor and distant metastases were collected for single-cell RNA sequencing and subsequent cell clustering, copy number variation (CNV) estimation, transcriptomic factor estimation, and pseudotime analyses. CNV analysis revealed that a small population of pretreatment cancer cells resisted chemotherapy and expanded. New clones including Metastatic Precursor Cells (MPCs), emerged in the posttreatment primary tumors in CNV similar to metastatic cells. MPCs exhibited expression profiles indicative of epithelial–mesenchymal transition. Comparison of MPCs with metastatic cancer cells also revealed dynamic changes in transcription factors and calcitonin pathway gene expression. These findings demonstrate the utility of single-patient clinical sample analysis for understanding tumor drug resistance, regrowth, and metastasis.

Abstract Background Cytomegalovirus (CMV) is the most common congenital infection in pregnancy with potential long-term adverse effects on the fetus. There is limited data on CMV seroprevalence in pregnant women in Singapore, with last reported study dating back over two decades. We look at the latest CMV seroprevalence in antenatal population in Singapore. Methods Between January 2021 and August 2021, 385 pregnant women receiving antenatal care at Singapore General Hospital were randomly selected for CMV IgG test to be performed on their blood samples collected during the first trimester of their pregnancies. Positivity for CMV IgG represents past exposure prior to pregnancy. Results Overall CMV seroprevalence was 71.7% (276/385) (95% CI 067, 0.76, p value

BackgroundHigh-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy.Case presentationWe report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy.ConclusionsIn this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy.

Camellia oleifera is a kind of high-quality oil supply species. Its seeds contain rich unsaturated fatty acids and antioxidant active ingredients, which is a kind of high-quality edible oil. In this study, we used bioinformatics methods to decipher a hexaploid Camellia oil tree’s mitochondrial (mt) genome based on second-generation sequencing data. A 709,596 bp circular map of C. oleifera mt genome was found for the first time. And 74 genes were annotated in the whole genome. Mt genomes of C. oleifera and three Theaceae species had regions with high similarity, including gene composition and gene sequence. At the same time, five conserved gene pairs were found in 20 species. In all of the mt genomes, most of nad genes existed in tandem pairs. In addition, the species classification result, which, according to the gene differences in tandem with nad5 genes, was consistent with the phylogenetic tree. These initial results provide a valuable basis for the further researches of Camellia oleifera and a reference for the systematic evolution of plant mt genomes.

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 recommendations, 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 preconception 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.

The composites of Mg20Pr1Sm3Y1Ni10 as-quenched alloy and 3 wt.% M (M = CoS, CoS2, MoS2) catalyst were prepared by high-speed vibration ball mill. The effects of metal sulfides on the hydrogenation and dehydrogenation dynamics of alloys were compared. The results show that the as-milled composites contain a large number of amorphous embedded by a small amount of nanocrystals, and there are many point defects. After ball milling, the crystal grain size in the composites containing CoS is relatively larger, followed by CoS2 and MoS2 again. After hydrogenation, the amorphous phase is crystallized to form Mg2NiH4, YH3, Pr8H18.96, Sm3H7, Mg, Co or Mo phases, however, Mg2Ni, YH2, PrH2 and Ni3Y phases appeared after dehydrogenation. The maximum hydrogenation capacity of the composites containing CoS, CoS2 and MoS2 are 3.939, 4.265 and 4.507 wt.%, respectively. The hydrogenation saturation ratio of composite containing MoS2 is higher than that of the composites containing CoS and CoS2. The dehydrogenation activation energy of the composites containing CoS, CoS2 and MoS2 is 107.76, 68.43 and 63.28 kJ.mol−1.H2. On the improvement of hydrogen storage performance of Mg20Pr1Sm3Y1Ni10 alloy, the catalytic effect of MoS2 sulfide is better than that of CoS2 sulfide, and which is better than CoS sulfide.

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.

Summary: 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.

Abstract Background Tissue-resident memory T (TRM) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of TRM cells but we know little about it. Methods Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of TRM cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a TRM-based spatial immune signature (TRM-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α). Results The density of TRM cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of TRM cell subsets was defined, including TRM1 (PD-1−Tim-3−TRM), TRM2 (PD-1+Tim-3−TRM), TRM3 (PD-1−Tim-3+TRM) and TRM4 (PD-1+Tim-3+TRM). The cytotoxicity of TRM2 was the strongest while that of TRM4 was the weakest. Compare with TRM1 and TRM2, TRM3 and TRM4 had better infiltration and stronger interaction with cancer cells. The TRM-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63–3.60), P

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 (

Abstract Background Cancer‐associated fibroblasts (CAFs) are a major stromal component of human breast cancers and often promote tumor proliferation, progression and malignancy. We previously established an experimental CAF (exp‐CAF) cell line equipped with a potent tumor‐promoting ability. It was generated through prolonged incubation of immortalized human mammary fibroblasts with human breast cancer cells in a tumor xenograft mouse model. Results Herein, we found that the exp‐CAFs highly express Runt‐related transcription factor 3 (RUNX3), while counterpart fibroblasts do not. In breast cancer patients, the proportion of RUNX3‐positive stromal fibroblast‐like cells tends to be higher in cancerous regions than in non‐cancerous regions. These findings suggest an association of RUNX3 with CAF characteristics in human breast cancers. To investigate the functional role of RUNX3 in CAFs, the exp‐CAFs with or without shRNA‐directed knockdown of RUNX3 were implanted with breast cancer cells subcutaneously in immunodeficient mice. Comparison of the resulting xenograft tumors revealed that tumor growth was significantly attenuated when RUNX3 expression was suppressed in the fibroblasts. Consistently, Ki‐67 and CD31 immunohistochemical staining of the tumor sections indicated reduction of cancer cell proliferation and microvessel formation in the tumors formed with the RUNX3‐suppressed exp‐CAFs. Conclusion These results suggest that increased RUNX3 expression could contribute to the tumor‐promoting ability of CAFs through mediating cancer cell growth and neoangiogenesis in human breast tumors.

Abstract Background The Knee Injury and Osteoarthritis Outcomes Score (KOOS) is a free clinical tool commonly used to evaluate the symptoms and functional status of patients with knee injury. For people who speak Chinese, the Hong Kong Chinese and Singapore Chinese versions are preferred. However, variations in the Chinese language and culture are influenced by the country’s geography. KOOS for Mainland China has not been reported. Therefore, the current study was to cross-culturally translate the original English version into a simplified Chinese version and to investigate its psychometric properties. Methods The simplified Chinese KOOS was obtained through forward-backward translation according to appropriate guidelines. A total of 158 individuals with knee osteoarthritis (KOA) were recruited from 13 hospitals in China to examine the psychometric properties. The test-retest questionnaire was performed at an interval of 5–7 days. Test-retest reliability and internal consistency were evaluated using the intraclass correlation coefficient (ICC) and Cronbach’s alpha, respectively. The data of the first test were used to analyse the construct validity of the simplified Chinese KOOS and Chinese SF-36 through convergent and discriminant validity using Spearman’s correlation coefficient. Results Cross-cultural translation exhibited minor cultural differences, and the questionnaire was well understood by the patients. The data from 128 patients, used for the test-retest reliability study, showed good to excellent reliability, with an ICC of 0.808–0.976 for all KOOS subscales. The Cronbach’s alpha for all subscales ranged from 0.757 to 0.970, indicating acceptable internal consistency. There was a low-to-high correlation between the five domains of the simplified Chinese version of the KOOS and all domains of the SF-36 in construct validity. Conclusion The simplified Chinese KOOS demonstrated acceptable reliability and validity. In clinical practice and research, this version can help provide valuable information on health-related quality of life for Chinese individuals with KOA in mainland China.

Abstract Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross‐sectional studies indicated certain motor and non‐motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed‐effect models were respectively conducted to investigate the cross‐sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross‐sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]‐adjusted p = 0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR‐adjusted p = 0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR‐adjusted p = 0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid‐eye‐movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR‐adjusted p = 0.0120). Furthermore, changes in MDS‐UPDRS scores and the State–Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p = 0.005 and p = 0.032, respectively). Our findings clarified quantitative associations between certain motor and non‐motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.

Abstract 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.

Abstract Background Anti-PD-(L)1 immunotherapy has been recommended for non-small cell lung cancer (NSCLC) patients with lymph node metastases (LNM). However, the exact functional feature and spatial architecture of tumor-infiltrating CD8 + T cells remain unclear in these patients. Methods Tissue microarrays (TMAs) from 279 IA-IIIB NSCLC samples were stained by multiplex immunofluorescence (mIF) for 11 markers (CD8, CD103, PD-1, Tim3, GZMB, CD4, Foxp3, CD31, αSMA, Hif-1α, pan-CK). We evaluated the density of CD8 + T-cell functional subsets, the mean nearest neighbor distance (mNND) between CD8 + T cells and neighboring cells, and the cancer-cell proximity score (CCPS) in invasive margin (IM) as well as tumor center (TC) to investigate their relationships with LNM and prognosis. Results The densities of CD8 + T-cell functional subsets, including predysfunctional CD8 + T cells (Tpredys) and dysfunctional CD8 + T cells (Tdys), in IM predominated over those in TC (P

To provide reference for the safety consumption of Phyllanthus acidus (PA) as food and its further medicinal development and utilization, a comparative study on acute and short-termtoxicity and α-glucosidase inhibitory ability of different components of its branches and leaves was conducted. The crude extract of PA, prepared under aqueous ethanol reflux extraction, was partitioned successively with petroleum ether, ethyl acetate and N-butanol according to the polarity. Furthermore, an alcohol-eluted and water-eluted fractions were obtained from water-soluble residue by column chromatography. The half inhibitory concentration (IC50) of α-glucosidase was used as the evaluation index to compare the in vitro hypoglycemic activity of different extracts. The acute toxicity of these fractions was screened by maximum tolerated dose (MTD), median lethal dose (LD50) values, and their subacute toxicity was evaluated by continuous oral administration of samples for 20 days. The results showed that each component of PA had a certain inhibitory ability to α-glucosidase. The MTD of crude extract of PA was 2.0 g/kg, and the order of acute toxicity for different fractions was ethanol-eluted fraction>water-eluted fraction>petroleum ether fraction>ethyl acetate fraction>N-butanol fraction>crude extract. The main acute toxicity symptoms were startle followed by idling, writhing, and shortness of breath. Subacute toxicity test showed no obvious toxicity and lesions. It was indicated that it was safe to take 2 g/kg/d (equivalent to 8.6 g/kg of dried branches and leaves) of the whole component of PA at oral ingestion. Thus, they have the potential to be developed as hypoglycemic, weight-loss food and medicine.

Abstract Background Residual somatic symptoms (RSS) are common in depressed patients, predicting treatment effectiveness. However, sex differences in RSS have received little systematic study. This study was conducted to compare sex differences of RSS in patients with first-episode depression (FED). Methods Nine hundred eighty-two patients with FED were selected and treated for 8 to 12 weeks. We evaluated the subjects' socio-demographic characteristics and residual depressive symptoms. Using the Patient Health Questionnaire-15 (PHQ-15) scale to assess residual somatic symptoms, the Sheehan Disability Scale (SDS) for the assessment of patients' function, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) for quality of life. Results The incidence of RSS with FED was 46.4%. For patients with residual symptoms, the age and age of onset in females were higher than males, but males had more years of education than females. The degree of "stomach pain" in females was more severe than in males, while "trouble sleeping" in males was more severe than that in females. Multiple regression analysis showed that the total Q-LES-Q-SF score was an independent influencing factor of RSS in both males and females, while the total SDS score only affected female RSS. Conclusions The prevalence of RSS in FED after acute-phase treatment is high. The symptom of "stomachache" is more pronounced in females, while "trouble sleeping" is more severe in males. Quality of life plays an essential role in RSS in both genders. Thus, sex needs to be considered when assessing the relationship between RSS and therapeutic effect in depression.

Abstract Background The intratumor heterogeneity (ITH) of cancer cells plays an important role in breast cancer resistance and recurrence. To develop better therapeutic strategies, it is necessary to understand the molecular mechanisms underlying ITH and their functional significance. Patient-derived organoids (PDOs) have recently been utilized in cancer research. They can also be used to study ITH as cancer cell diversity is thought to be maintained within the organoid line. However, no reports investigated intratumor transcriptomic heterogeneity in organoids derived from patients with breast cancer. This study aimed to investigate transcriptomic ITH in breast cancer PDOs. Methods We established PDO lines from ten patients with breast cancer and performed single-cell transcriptomic analysis. First, we clustered cancer cells for each PDO using the Seurat package. Then, we defined and compared the cluster-specific gene signature (ClustGS) corresponding to each cell cluster in each PDO. Results Cancer cells were clustered into 3–6 cell populations with distinct cellular states in each PDO line. We identified 38 clusters with ClustGS in 10 PDO lines and used Jaccard similarity index to compare the similarity of these signatures. We found that 29 signatures could be categorized into 7 shared meta-ClustGSs, such as those related to the cell cycle or epithelial–mesenchymal transition, and 9 signatures were unique to single PDO lines. These unique cell populations appeared to represent the characteristics of the original tumors derived from patients. Conclusions We confirmed the existence of transcriptomic ITH in breast cancer PDOs. Some cellular states were commonly observed in multiple PDOs, whereas others were specific to single PDO lines. The combination of these shared and unique cellular states formed the ITH of each PDO.

Abstract Background Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen and has emerged as one of the most troublesome pathogens. Drug resistance in A. baumannii has been reported on a global scale. Minocycline was found to be active against multi-drug resistant A. baumannii and was approved by the FDA for the infections caused by sensitive strains of A. baumannii. However, the emergence of minocycline resistance and its toxic effects still need to be addressed. Therefore, this study aimed to evaluate the synergistic effects of metformin combined with minocycline on minocycline-resistant A. baumannii. Results The effect of metformin on the antibacterial activity of minocycline was determined by checkerboard and time-killing assay. Further, it was observed by biofilm formation assay that metformin combination with minocycline can inhibit the formation of biofilm. Outer membrane integrity, membrane permeability, membrane potential and reactive oxygen species (ROS) were monitored to explore the underlying synergistic mechanisms of metformin on minocycline. And the results shown that metformin can destroy the outer membrane of A. baumannii, enhance its membrane potential, but does not affect the membrane permeability and ROS. Conclusion These findings suggested that the combination of metformin and minocycline has the potential for rejuvenating the activity of minocycline against minocycline-resistant A. baumannii.

ObjectiveThe incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD.MethodsWe recruited 1,289 FEDN MDD patients aged 18 ~ 45 years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression.ResultsThe prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD.LimitationsNo causal relationship can be drawn due to the cross-sectional design.ConclusionTD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD.

In this paper, the polysaccharides fingerprints of Polygonatum cyrtonema Hua. were constructed, combined with various chemometric methods, to evaluate the differences of P. cyrtonema polysaccharides from different origins. The 1-pheny-3-methyl-5-pyrazolone (PMP) pre-column derivatization-HPLC method was applied to analyze the monosaccharide composition and total polysaccharide content of P. cyrtonema. Furthermore, the fingerprints were further evaluated by chemometric methods, including similarity analysis (SA), cluster analysis (HCA), and principal component analysis (PCA). The results showed that the composition of monosaccharides was galacturonic acid, glucuronic acid, galactose, glucose, and xylose. The similarities were ranged from 0.781 to 0.945. In addition, the content of total polysaccharides was in the range of 7.18% to 16.27%. HCA and PCA all divided P. cyrtonema polysaccharides from different origins into two categories, the samples collected in Cili County, Hunan Province were a separate one. These results indicated that the polysaccharide fingerprints of P. cyrtonema were quite different. Establishing the standardized cultivation technology system of P. cyrtonema is necessary to ensure clinical efficacy and safety.

Abstract In breast cancer patients, tumor heterogeneity is associated with prognosis and therapeutic response; however, the epigenetic diversity that exists in primary tumors remains unknown. Using a single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), we obtained the chromatin accessibility profiles of 12,452 cells from 16 breast cancer patients including 11 luminal, 1 luminal-HER2, 1 HER2+, and 3 triple-negative subtypes. Via this profiling process, tumors were classified into cancer cells and the tumor microenvironment, highlighting the heterogeneity of disease-related pathways including estrogen receptor (ER) signaling. Furthermore, the coexistence of cancer cell clusters with different ER binding motif enrichments was identified in a single ER+ tumor. In a cluster with reduced ER motif enrichment, we identified GRHL2, a transcription factor, as the most enriched motif, and it cooperated with FOXA1 to initiate endocrine resistance. Coaccessibility analysis revealed that GRHL2 binding elements potentially regulate genes associated with endocrine resistance, metastasis, and poor prognosis in patients that received hormonal therapy. Overall, our study suggests that epigenetic heterogeneity could lead to endocrine resistance and poor prognosis in breast cancer patients and it offers a large-scale resource for further cancer research.

Breast cancer biology varies markedly among patients. Basal-like breast cancer is one of the most challenging subtypes to treat because it lacks effective therapeutic targets. Despite numerous studies on potential targetable molecules in this subtype, few targets have shown promise. However, the present study revealed that FOXD1, a transcription factor that functions in both normal development and malignancy, is associated with poor prognosis in basal-like breast cancer. We analyzed publicly available RNA sequencing data and conducted FOXD1-knockdown experiments, finding that FOXD1 maintains gene expression programs that contribute to tumor progression. We first conducted survival analysis of patients grouped via a Gaussian mixture model based on gene expression in basal-like tumors, finding that FOXD1 is a prognostic factor specific to this subtype. Then, our RNA sequencing and chromatin immunoprecipitation sequencing experiments using the basal-like breast cancer cell lines BT549 and Hs578T with FOXD1 knockdown revealed that FOXD1 regulates enhancer–gene programs related to tumor progression. These findings suggest that FOXD1 plays an important role in basal-like breast cancer progression and may represent a promising therapeutic target.

IntroductionThe formation of color in plants is significantly dependent on anthocyaninpigments. Grape species vary in color due to the differences in anthocyanin accumulation. It is widely recognized that both biotic and abiotic conditions may have an impact on anthocyanin synthesis in plants. The underlying molecular mechanisms by which external application of hyperoside impacts anthocyanin formation in grapes, however, have received little attention.MethodsIn the current study,the transcriptome of Gemstone seedless grape was examined using high-throughput RNA sequencing at various developmental stages reply to both control and hyperoside treatments.ResultsThe results of this study suggested that the major genes controlling anthocyanin accumulation in response to the externalinjection of hyperoside could be VvMYB62, VvPAL, VvCHS, and VvF3’5’H.Quantitative reverse transcription PCR (RT-qPCR) results were used to confirm the changes in the expression levels of the genes encoding the anthocyanin biosynthesis pathway under the control and hyperoside treatments. Using a transient transformation system, it was discovered that VvMYB62 was shown to regulate the anthocyanin accumulation at both the transcriptional and posttranslational levels and could be influenced by the external administration of hyperoside. In grape embryogenic calli, hyperoside could specifically suppress theexpression of VvMYB62 and anthocyanin accumulation. In this instance, the VvMYB62 characterisation brought attention to the significance of exogenous hyperoside-induced anthocyanin accumulation. Therefore, the results demonstrated that VvMYB62 could be hindered in the process of grape during anthocyanin accumulation caused by hyperoside.DiscussionThese findings offer excellent candidate genes in the future breeding of novel grape varieties in addition to serving as a crucial reference for understanding the underlying molecular processes of hyperoside suppression of anthocyanin formation in plants.

This paper discusses sub-base local reducts in a family of sub-bases. Firstly, definitions of sub-base local consistent sets and sub-base local reducts are provided. Using the sub-base local discernibility matrix, a necessary and sufficient condition for sub-base local consistent sets is presented. Secondly, properties of the sub-base local core are studied. Finally, sub-base local discernibility Boolean matrices are defined, and the calculation method is given. Utilizing sub-base local discernibility Boolean matrices, an algorithm is devised to obtain sub-base local reducts.

As an important part of the lava flow reservoir, vesicles affect reservoir performance to some extent. To explore the distribution, origins and importance of vesicles in different facies belts of basic lava flows. In this study, we selected representative field outcrops and samples from different facies belts of the Laoheishan and Huoshaoshan lava flows in the Wudalianchi volcanics, Heilongjiang Province, identified and examined vesicles, measured their porosity and permeability, and analyzed their surface porosity. Three facies belts of vesicle shape, size, quantity, arrangement, origin, and connectivity between vesicles and fractures were identified. The results showed that the vesicles in the crater–near-crater belt were ellipsoidal and spherical, with many vesicles. The vesicles in the proximal belt were dominated by many ellipsoids with a uniform distribution. The vesicles in the distal belt were dominated by spherical and ellipsoidal vesicles, with a few tubular vesicles and a small number of vesicles. The findings suggest that the crater-near-crater belt and proximal belt have the best reservoir performance, whereas the distal belt has the worst.

Recently, many scholars have conducted experimental mechanical compaction studies on sandstones, carbonates, and mudstones to visually study the mechanical compaction process and reservoir evolution of sedimentary rocks. However, experimental mechanical compaction studies on the evolution of the compaction process of pyroclastic rocks have been ignored. Volcaniclastic rock reservoirs are widely distributed across the world and strongly influenced by the crushing of pyroclastic particles. In this study, we analyzed the characteristics and controlling factors of the crushing of pyroclastic particles during compaction diagenesis from a microscopic perspective through experimental mechanical compaction. These results can provide quantitative compaction background parameters for the quantitative study of pyroclastic rock reservoir evolution. We took pyroclastic samples from Hongtu Hill in the Changbaishan area as an example, and experimental mechanical compaction experiments were conducted. Furthermore, image surface porosity and particle analysis statistical methods were used, and the variations in the effective porosity and image surface porosity under different axial stresses were studied. The results showed that, after compaction, the effective porosity did not exhibit a decreasing trend with increasing axial stress but rather a normal distribution trend that initially increased and then decreased. In the compaction experiment, the pyroclastic particle crushing process was segmented with increasing axial stress, and there was an obvious compaction band in the initial stage of the compaction, called the particle rearrangement stage (10–30 MPa). Furthermore, there were relatively non-successive compaction localization areas in the later stage of compaction, called the particle crushing stage (50–70 MPa), which was represented by vitreous basalt particles surrounded by porphyritic basalt particles. During experimental mechanical compaction, the smaller the compactness, the smaller the solidity, and the larger the slenderness of the particles, the more likely the particles were to break during compaction. Particles containing intragranular pores and vitreous basalt particles were easily crushed.

BackgroundThe anti-tumoral or pro-tumoral roles of CD4+ and CD8+ T cells typify the complexity of T cell subsets function in cancer. In the non-small cell lung cancer (NSCLC), the density and topology of distinct T cell phenotypes at the tumor center (TC) versus the invasive margin (IM) are largely unknown. Here, we investigated T cell subsets density and distribution within TC and IM regions in NSCLC and its impact on the prognosis.MethodsWe performed multiplex immunofluorescence using a tissue microarray of samples from 99 patients with locally advanced NSCLC to elucidate the distributions of tumor cell, T cell subpopulations (CD4/conventional CD4/regulatory CD4/CD8/cytotoxic CD8/pre-dysfunctional CD8/dysfunctional CD8), microvessel density (MVD), cancer-associated fibroblasts (CAFs) and hypoxia-inducible factor-1α (HIF-1α) in TC and IM tissues. Cell-to-cell nearest neighbor distances and interactions were analyzed using the phenoptrreports R package. Cox regression was used to evaluate the associations between T cell subsets density and proximity to tumor cells and recurrence-free survival (RFS). Correlations between different cell subsets were examined by Spearman’s or Kruskal-Wallis tests.ResultsIn the locally advanced NSCLC, the proportion of tumor cells and CAFs in IM is lower than in the TC, while MVD, CD4+, and CD8+ T lymphocytes were increased, and tumor cells were closer to T lymphocytes and their subsets. The density and proximity of CD4+ and CD8+ T cells in the TC and IM regions were not associated with RFS, but in the IM area, increased density of dysfunctional CD8 and closer regulatory CD4 to tumor cells were independent risk factors for recurrence (HR were 3.536 and 2.884, respectively), and were positively correlated with HIF-1α+CD8 (r = 0.41, P = 0.000) and CAFs (P = 0.017), respectively.sConclusionsIn locally advanced NSCLC, the functional status of T cells in the IM region is closely related to recurrence. The density of dysfunctional CD8 and the proximity of regulatory CD4 to tumor cells were independent risk factors for recurrence, and are positively correlated with the hypoxia response of CD8+ T cells and CAFs. Targeting hypoxia or CAFs is expected to further sensitize therapy.

Bioaerosol is a new type of pollutant, which is related to the spread of many diseases. In particular, the bioaerosol produced in the hospital sewage treatment process contains many pathogenic bacteria, which will impact patients and surrounding residents. In this study, the biochemical tank (BRT) of the hospital sewage treatment station (HSTS) and municipal wastewater treatment plant (MWTP) were used as sampling points. The results showed that the concentration of bacteria (1843 CFU/m3) in bioaerosol produced by BRT of HSTS was higher than that in the air at BRT of MWTP (1278 CFU/m3). The proportion of small-size bacteria (

Multirotor UAVs are becoming increasingly important in both civilian and military fields. In the plateau environment, the endurance time of multirotor UAVs is still too short for mission requirements. Thus, the optimisation of the efficiency of the power system is considered to be an effective way to overcome this problem. This paper presents a practical method of power system design to maximise endurance time in a plateau environment. First, the optimal proportion of battery quality is analysed from the perspective of energy consumption of multirotor UAVs. Second, the modelling method of each component of the power system is studied separately. Then, the endurance solution method is given, the multirotor UAV power system is optimised and analysed according to the given design requirements, and the effectiveness and practicability of the method are verified through experiments.

Aims: Human breast milk remains an important source of protection against infection, inflammation, allergy and long-term metabolic disorders for the breastfed offspring. During cases of ongoing infection, the dilemma faced by both medical health professionals and mothers is the need to balance the risk of continuing versus temporarily or permanently ceasing to breastfeed. The aim of our article is to review existing literature regarding breastfeeding during acute infectious and non-infectious illnesses and to provide feasible evidence-based suggestions which can be implemented by medical practitioners during counselling of breastfeeding mothers. Method: A literature search was conducted on PubMed (US National Library of Medicine) using various combinations of keywords related to breastfeeding and the various infections. The citations from all selected articles were reviewed for additional studies. Results: Most ongoing infections are not contraindications for breastfeeding, with the exceptions of Human Immunodeficiency viruses (HIV), Human T-cell lymphotropic virus (HTLV) types 1 and 2. Even with HIV, there is increasing evidence to reassure that with adequate antiretroviral therapy, breastfeeding is likely to be safe. Of particular concern during the COVID-19 pandemic too, current evidence indicates that mothers with COVID-19 infection can safely breastfeed, and therefore initiation and continuation of breastfeeding should continue to protect the health of the babies and mothers. Conclusion: During this pandemic especially, there is a strong and urgent need to support mothers with acute infections who wish to breastfeed. With better awareness, physicians can play an important role in securing positive experiences for breastfeeding mothers and optimizing infant outcomes.

Bioaerosols can be generated in wastewater treatment plants (WWTPs), they may contain pathogenic bacteria, cause disease transmission, and attract the public’s attention. In this study, bioaerosols were collected from seven different stages of an A²O process WWTP. The component characteristics were analyzed by bacterial culture and high-throughput sequencing. The correlations in different processes were analyzed, and the health risks of bioaerosols produced were evaluated. The results showed that the concentration range of bacteria aerosol in the WWTP was 75 CFU/m³−706 CFU/m³. The concentration range of total suspended particles was 111.13 µg/m³−211.67 µg/m³, the primary water-soluble ions were Ca²⁺ and Cl⁻. In the air of each stage, the main bacteria were Cetobacterium, Bacteroides, Romboutsia, and the fungi were Fusarium, Alternaria, and Aspergillus. The dominant bacteria in the wastewater were Cetobacterium, Romboutsia, Stenotrophobacter, and the fungi were Fusarium, Aspergillus, and Mortierella. The total bacterial concentration and ion concentration in the aerobic section of the biochemical tank were the highest. The results of species composition and principal component analysis showed that the bacterial composition in the air at different processes was similar, while the bacteria in wastewater differed significantly. Among them, the wastewater bacteria in the aerobic section of the biochemical tank were closer to that in the air. Fungal results were similar to bacteria but not prominent. The bioaerosol exposure risk results show that the risk in each stage was acceptable (5.15 ×10⁻⁴−6.47 ×10⁻³). However, the exposure risk of bioaerosol was calculated by the total bacterial concentration. In fact, some pathogenic microorganisms such as Escherichia coli and Aspergillus flavus were detected in bioaerosols, which may cause hemorrhagic colitis, cancer and other diseases by swallowing and inhalation. Therefore, the risk might be underestimated and should be a cause of concern.

Azadirachtin is one of the most successful botanical pesticides in agricultural pest control. To build a repertoire of proteins and pathways in response to azadirachtin exposure during ovarian development, iTRAQ-based comparative proteomic was conducted. 1423 and 1686 proteins were identified as differentially accumulated proteins (DAPs) by comparing the protein abundance in adult ovary with that in pupal ovary under normal and azadirachtin exposure condition, respectively. Bioinformatics analysis indicated that pupae-to-adult transition requires proteins related to proteasome and branched chain amino acids (BCAAs) degradation for ovary development. Azadirachtin exposure strongly affected glycosylation-related pathway. And proteins related to vitamin B6 synthesis were necessary for ovary development under normal and AZA-exposure condition. RNAi assays confirmed the essential roles of DAPs related to glycosylation and vitamin B6 synthesis in moth growth and ovary development. The results enhance our understanding of the molecular regulatory network for ovary development and provide valuable resources for using AZA-responsive proteins to develop novel bio-rational insecticides.

The treatment of patients with glioma still faces many difficulties. To further optimize treatment, it is necessary to identify more accurate markers as treatment targets and predict prognostic indicators. RNASE2 was identified as a differentially expressed gene (DEG) in glioma tissues using bioinformatics analysis. In glioma microarrays, 31.21% (54/173) and 68.79% (119/173) patients showed low and high RNASE2 protein expression levels, respectively. RNASE2 protein levels were considerably correlated with age, WHO grade, relapse, and death. Both mRNA and protein levels were associated with the overall survival of patients with glioma. To investigate the role of RNASE2, it was overexpressed or silenced in glioma cells. RNASE2 overexpression promoted cell proliferation, migration, and invasion. In addition, its overexpression promoted the growth of subcutaneous tumors and lung metastasis of glioma cells. Key protein levels in the PI3K/Akt signaling pathway were upregulated by RNASE2 overexpression. In contrast, RNASE2 knockdown had the opposite effects. Furthermore, LY294002 blocked the effects of RNASE2 on the cell function of glioma cells. In conclusion, RNASE2 is a novel marker associated with the diagnosis and prognosis of patients with glioma, and it promotes the malignant progression of gliomas through the PI3K/Akt signaling pathway.

Abstract Background The grass-roots civil servants are the final implementers and executors of a series of government policies and the fundamental force for social stability and harmonious development. However, the mental health problems of grass-roots civil servants have not got full attention. This study aimed to assess the impact of resilience on anxiety and depression among grass-roots civil servants in China. Method From Oct to Dec 2019, 302 civil servants completed a series of questionnaires. The Civil Servants Stress Scale (CSSS) was used to assess the stress of civil servants. The Self-rating Depression Scale (SDS) and the Self-rating Anxiety Scale (SAS) were used to evaluate the depression and anxiety of participants, respectively. The resilience of civil servants evaluates by the Connor-Davidson Resilience Scale (CD-RSCI). We conducted the moderating and mediating analysis on the impact of resilience on depression and anxiety in grass-roots civil servants. Results There were significant differences in gender, education, position, relationship with coworkers, physical exercise, and monthly income for stress in grass-roots civil servants (P

Abstract The aim of this study was to carry out a case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma (OC-SCC) to normal patients using metagenomic shotgun sequencing. We recruited 50 OC-SCC cases which were then matched with a control patient by age, gender, race, smoking status and alcohol status. DNA was extracted from oral wash samples from all patients and whole genome shotgun sequencing performed. The raw sequence data was cleaned, reads aligned with the human genome (GRCH38), nonhuman reads identified and then HPV genotypes identified using HPViewer. In the 50 patients with OC-SCC, the most common subsite was tongue in 26 (52%). All patients were treated with primary resection and neck dissection. All but 2 tumors were negative on p16 immunohistochemistry. There were no statistically significant differences between the cases and controls in terms of gender, age, race/ethnicity, alcohol drinking, and cigarette smoking. There was no statistically significant difference between the cancer samples and control samples in the nonhuman DNA reads (medians 4,228,072 vs. 5,719,715, P value = 0.324). HPV was detected in 5 cases (10%) of OC-SCC (genotypes 10, 16, 98) but only 1 tumor sample (genotype 16) yielded a high number of reads to suggest a role in the etiology of OC-SCC. HPV was detected in 4 control patients (genotypes 16, 22, 76, 200) but all had only 1–2 HPV reads per human genome. Genotypes of HPV are rarely found in patients with oral cancer.

Emotion can be defined as a subject’s organismic response to an external or internal stimulus event. The responses could be reflected in pattern changes of the subject’s facial expression, gesture, gait, eye-movement, physiological signals, speech and voice, keystroke, and mouse dynamics, etc. This suggests that on the one hand emotions can be measured/recognized from the responses, and on the other hand they can be facilitated/regulated by external stimulus events, situation changes or internal motivation changes. It is well-known that emotion has a close relationship with both physical and mental health, usually affecting an individual’s and a team’s work performance, thus emotion recognition is an important prerequisite for emotion regulation towards better emotional states and work performance. The primary problem in emotion recognition is how to recognize a subject’s emotional states easily and accurately. Currently, there are a body of good research on emotion recognition from facial expression, gesture, gait, eye-tracking, and other physiological signals such as speech and voice, but they are all intrusive and obtrusive to some extent. In contrast, keystroke, mouse and touchscreen (KMT) dynamics data can be collected non-intrusively and unobtrusively as secondary data responding to primary physical actions, thus, this paper aims to review the state-of-the-art research on emotion recognition from KMT dynamics and to identify key research challenges, opportunities and a future research roadmap for referencing. In addition, this paper answers the following six research questions (RQs): (1) what are the commonly used emotion elicitation methods and databases for emotion recognition? (2) which emotions could be recognized from KMT dynamics? (3) what key features are most appropriate for recognizing different specific emotions? (4) which classification methods are most effective for specific emotions? (5) what are the application trends of emotion recognition from KMT dynamics? (6) which application contexts are of greatest concern?

Bioaerosols containing pathogens released from wastewater treatment plants (WWTP) may pose potential health risks to workers on-site and residents downwind. In this study, sampling points were set up in the wastewater treatment facility to investigate the generation pattern of bioaerosols in the aeration tank section. High-throughput sequencing was utilized to assay the intestinal bacteria population, while the health risks associated with airborne bacteria were estimated based on average daily dose rates. The contribution of wastewater to bioaerosols was evaluated using the traceability analysis. As the rotational speed increased from 200 rpm to 800 rpm, the concentration of culturable bacteria increased from 397 CFU/m3 to 1611 CFU/m3, the proportion of bacteria attached to particles with an aerodynamic diameter larger than 4.7 µm increased from 30.41% to 48.44%, and the Shannon index of air samples increased from 1.032485 to 1.282065. Microbial composition, sources, and health risks of bioaerosols also changed as the rotational speed increased. The results showed that the predominant bacteria in the air at 200 rpm were Bacillus (78.78%), Paenibacillus (11.77%) and Lysinibacillus (1.40%). When the rotating speed reached 800 rpm, the dominant bacteria became Bacillus (55.50%), Acinetobacter (31.01%), and Paenarthrobacter (13.17%). The contribution of the wastewater to bioaerosols increased from 46.49% to 65.10%, in which surface water was the main source of bioaerosols (34.64% on average). Although the contribution of bottom water was lower than that of surface water, its contribution increased more, from 15.36% to 29.31%. The health risk of bioaerosols was 1.28 × 10−2 on average, which increased with the increase of rotational speed. At the same exposure concentration, children (2.31 × 10−2) have a higher exposure risk than adults (7.67 × 10−3). This study is aimed at exploring the variation law of bioaerosols discharged from WWTP with oxidation ditch process and providing preliminary data for reducing its risk.

Abstract Conductive fabrics are promising candidates for developing flexible, lightweight, and high conductivity electromagnetic (EM) shielding materials to meet the requirements of next‐generation flexible and wearable electronics. Herein, an effective strategy to construct a conductive titanium carbide (Ti3C2Tx)/Polyaniline (PANI) composite with 3D nanoflower structure by deposition of PANI on the surface of single‐layer Ti3C2Tx nanosheets through in situ and oxidant‐free polymerization of aniline monomer to avoid the restacking/aggregation and easy oxidation of Ti3C2Tx MXene is developed. In addition, GaIn liquid metal (LM) nanoparticles are also incorporated into the Ti3C2Tx/PANI microsphere to increase conductivity and stability. This method solves the existing problems of poor connectivity between LM nanoparticles and discontinuity of the Ti3C2Tx MXene nanosheets. Eventually, by using carbon fabrics (CF) as the substrate, a flexible, stable, and efficient electromagnetic interference (EMI) shielding conductive composite fabric with an optimal EMI shielding efficiency (EMI SE) value of 52.0 dB in the range of 8.2–12.4 GHz at a thickness of 0.27 mm is developed. Meanwhile, the as‐prepared fabrics demonstrate superior Joule heating property, high mechanical flexibility, and excellent bending‐release stability. The study provides a simple and efficient method to fabricate multifunctional conductive textiles to meet the need for practical application in EMI shielding area.

BackgroundLong-term excessive use of morphine leads to addictive diseases and affects cognitive function. Cognitive performance is associated with genetic characteristics.MiR-124 plays a critical regulatory role in neurogenesis, synaptic development, brain plasticity, and the use of addictive substances. As a scaffold protein, IQGAP1 affects learning and memory dose-dependent. However, the role of miR-124 and its target protein as potential addiction biomarkers and the impact on cognitive function have not been fully explored.MethodA total of 40 patients with morphine dependence and 40 cases of healthy people were recruited. We collected basic and clinical information about the two groups. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9(PHQ-9), Montreal Cognition Assessment Scale (MoCA), Pittsburgh Sleep Quality Index (PSQI) were used to assess the severity of depression, anxiety, depressive symptoms, cognitive dysfunction, and sleep quality.ResultsCompared to the control group, the morphine-dependent group had higher GAD-7, PHQ-9, PSQI scores, and more elevated miR-124 levels but lower MOCA scores and IQGAP1 levels. MiR-124, IQGAP1, the average intake last year were related to OASI scores.MiR-124, IQGAP1, PHQ-9 were associated with MOCA scores. In the multiple regression model, the levels of miR-124 and IQGAP1 were independent factors influencing the severity of morphine dependence. The level of miR-124 was an independent factor influencing the severity of cognitive impairment in patients with morphine dependence. In addition, the luciferase report confirmed that IQGAP1 mRNA is the direct target of miR-124.ConclusionMiR-124 and its target protein IQGAP1 are involved in the regulation of addiction and cognitive function in patients with morphine dependence.

Abstract Background COVID-19 may predispose pregnant women to higher risks of severe disease and poorer neonatal outcome. Psychological sequalae of this pandemic may pose a greater conundrum than its clinical aspects. It is currently unknown that how pregnant women cope with this global pandemic and its ramifications. The aims of the study are to understand the attitudes and precaution practices of non-infected pregnant women towards the COVID-19 outbreak in Singapore. Methods An online cross-sectional survey of COVID-19 awareness among pregnant women attending antenatal clinics in Singapore was conducted. An internet link was provided to complete an online electronic survey on Google platform using a quick response (QR) code on mobile devices. The online survey consists of 34 questions that were categorized into 4 main sections, namely 1) social demographics 2) attitude on safe distancing measures 3) precaution practices and 4) perceptions of COVID-19. Multiple linear regression analysis was performed to examine women’s precaution practices among six independent socio-demographic variables, including age, ethnicity, education, front-line jobs, history of miscarriage and type of antenatal clinic (general, high risk). Results A total of 167 survey responses were obtained over 8 weeks from April to June 2020. The majority of women were aged ≤35 years (76%, n = 127), were of Chinese ethnicity (55%, n = 91), attained tertiary education (62%, n = 104) and were not working as frontline staff (70%). Using multiple linear regression models, Malay ethnicity (vs. Chinese, β 0.24; 95% CI 0.04, 0.44) was associated with higher frequency of practicing social distancing. Malay women (β 0.48; 95% CI 0.16, 0.80) and those who worked as frontline staff (β 0.28; 95% CI 0.01, 0.56) sanitized their hands at higher frequencies. Age of ≥36 years (vs. ≤30 years, β 0.24; 95% CI 0.01, 0.46), Malay (vs. Chinese, β 0.27; 95% CI 0.06, 0.48) and Indian ethnicity (vs. Chinese, β 0.41; 95% CI 0.02, 0.80), and attendance at high-risk clinic (vs. general clinic, β 0.20; 95% CI 0.01, 0.39) were associated with higher frequency of staying-at-home. Conclusion Social demographical factors including age > 36 years old, Malay ethnicity, employment in front line jobs and attendance at high-risk clinics are likely to influence the attitudes and precaution practices among pregnant women towards COVID-19 in Singapore. Knowledge gained from our cross-sectional online survey can better guide clinicians to communicate better with pregnant women. Hence, it is important for clinicians to render appropriate counselling and focused clarification on the effect of COVID-19 among pregnant women for psychological support and mental well being.

Abstract Background Non-invasive prenatal testing (NIPT) has revolutionized the prenatal screening landscape with its high accuracy and low false positive rate for detecting Trisomy 21, 18 and 13. Good understanding of its benefits and limitations is crucial for obstetricians to provide effective counselling and make informed decisions about its use. This study aimed to evaluate obstetrician knowledge and attitudes regarding NIPT for screening for the common trisomies, explore how obstetricians integrated NIPT into first-line and contingent screening, and determine whether expanded use of NIPT to screen for sex chromosome aneuploidies (SCAs) and microdeletion/microduplication syndromes (CNVs) was widespread. Methods A questionnaire was designed and administered with reference to the CHERRIES criteria for online surveys. Doctors on the Obstetrics & Gynaecology trainee and specialist registers were invited to participate. Medians and 95% confidence intervals (CI) were reported for confidence and knowledge scores. Results 94/306 (30.7%) doctors responded to the survey. First trimester screening (FTS) remained the main method offered to screen for the common trisomies. 45.7% (43/94) offered NIPT as an alternative first-line screen for singletons and 30.9% (29/94) for monochorionic diamniotic twins. A significant proportion offered concurrent NT and NIPT (25/94, 26.6%), or FTS and NIPT (33/94, 35.1%) in singletons. Varying follow up strategies were offered at intermediate, high and very-high FTS risk cut-offs for Trisomy 21. Respondents were likely to offer screening for SCAs and CNVs to give patients autonomy of choice (53/94, 56.4% SCAs, 47/94, 50% CNVs) at no additional cost (52/94, 55.3% SCAs, 39/94, 41.5% CNVs). Median clinical knowledge scores were high (10/12) and did not differ significantly between specialists (95% CI 10–11) and non-specialists (95% CI 9.89–11). Lower scores were observed for scenarios in which NIPT would be more likely to fail. Conclusions Our findings show the diversity of clinical practice with regard to the incorporation of NIPT into prenatal screening algorithms, and suggest that the use of NIPT both as a first-line screening tool in the general obstetric population, and to screen for SCAs and CNVs, is becoming increasingly prevalent. Clear guidance and continuing educational support are essential for providers in this rapidly evolving field.

Our objective was to investigate the relationship between the gut microbiota and anthropometric measurements among 248 participants from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Our cohort represents a unique population that allows for the investigation of the gut microbiota and anthropometric measurements in lean individuals. We measured height, weight, arm, thigh, hip, and waist circumferences, and collected fecal samples. Microbial DNA was extracted from the stool samples and sequenced by 16S rRNA gene sequencing. We examined associations between relative abundance of individual bacterial taxa from phylum to genus levels and anthropometric measurements. We found that higher BMI, mid-upper arm circumference, waist circumference, and waist-to-hip ratio were associated with a lower alpha diversity of fecal bacteria. Relative abundance of the genus Oscillospira and the family S24-7 were inversely related to all measurements after correction for multiple testing. Relative abundance of genus Acidaminococcus and family Ruminococcaceae were also associated with several measurements. The positive associations of the genus Acidaminococcus with BMI, as well as waist and hip circumferences, were stronger in women than in men. Our data in this lean Bangladeshi population found a correlation between Oscillospira and leanness, as measured using multiple anthropometric measures.

Given the payload limitation of unmanned aerial vehicles (UAVs), lightweight sensors such as camera, inertial measurement unit (IMU), and GPS, are ideal onboard measurement devices. By fusing multiple sensors, accurate state estimations can be achieved. Robustness against sensor faults is also possible because of redundancy. However, scale estimation of visual systems (visual odometry or visual inertial odometry, VO/VIO) suffers from sensor noise and special-case movements such as uniform linear motion. Thus, in this paper, a scale insensitive multi-sensor fusion (SIMSF) framework based on graph optimization is proposed. This framework combines the local estimation of the VO/VIO and global sensors to infer the accurate global state estimation of UAVs in real time. A similarity transformation between the local frame of the VO/VIO and the global frame is estimated by optimizing the poses of the most recent UAV states. In particular, for VO, an initial scale is estimated by aligning the VO with the IMU and GPS measurements. Moreover, a fault detection method for VO/VIO is also proposed to enhance the robustness of the fusion framework. The proposed methods are tested on a UAV platform and evaluated in several challenging environments. A comparison between our results and the results from other state-of-the-art algorithms demonstrate the superior accuracy, robustness, and real-time performance of our system. Our work is also a general fusion framework, which can be extended to other platforms as well.

Effective management of public opinion on the doctor-patient relationship network is an important element of maintaining social harmony and stability. In this paper, a new tripartite evolutionary game is proposed, the purpose of which is to examine the behavioral strategies of doctors, governments and netizens in the evolution of public opinion on the doctor-patient relationship network. Secondly, we further propose evolutionary replication dynamics equations in order to study the evolutionary stable strategies of participants. Select Shaanxi “Yulin puerpera fall from a building” as a case study, the applicability of the method was demonstrated and the main factors affecting the behavior of participants were found. Finally, we put forward suggestions on the management and control of public opinion on the doctor-patient relationship network from the four perspectives of doctors, government, media, and netizens. Research shows that the development of public opinion on the doctor-patient relationship network is the result of the joint action of multiple participants.

To cultivate different grape varieties according to market needs, it is necessary to study the regulation mechanism of color changes in different development stages of grapes. In this study, RNA-sequencing (RNA-Seq) technology was used to compare and analyze the transcriptome data of four grape varieties at the same development stage. Among the annotated differential genes, the anthocyanin synthesis pathway in the flavonoid pathway was mainly studied. Further RT-qPCR analysis of key enzyme genes, in the flavonoid synthesis pathway of the anthocyanin metabolism pathway, showed that the MYB transcription factor family had binding sites at the start of the four enzyme genes. The relative expression of the MYB transcription factor and enzyme gene in the transcriptome data was verified by reverse transcription polymerase chain reaction. Subcellular localization and gene function verification of the transcription factor MYB2 confirmed its regulatory role in anthocyanins.

Acinetobacter baumannii is an opportunistic pathogen predominantly associated with nosocomial infections. With emerging resistance against polymyxins, synergistic combinations of drugs are being investigated as a new therapeutic approach. Capsaicin is a common constituent of the human diet and is widely used in traditional alternative medicines. The present study evaluated the antibacterial activities of capsaicin in combination with colistin against three unrelated colistin-resistant Acinetobacter baumannii strains in vitro and in vivo, and then further studied their synergistic mechanisms. Using the checkerboard technique and time-kill assays, capsaicin and colistin showed a synergistic effect on colistin-resistant A. baumannii. A mouse bacteremia model confirmed the in vivo effects of capsaicin and colistin. Mechanistic studies shown that capsaicin can inhibit the biofilm formation of both colistin-resistant and non-resistant A. baumannii. In addition, capsaicin decreased the production of intracellular ATP and disrupted the outer membrane of A. baumannii. In summary, the synergy between these drugs may enable a lower concentration of colistin to be used to treat A. baumannii infection, thereby reducing the dose-dependent side effects. Hence, capsaicin–colistin combination therapy may offer a new treatment option for the control of A. baumannii infection.

The CRISPR-Cas system is a bacterial and archaea adaptive immune system and is a newly recognized mechanism for controlling antibiotic resistance gene transfer. Acinetobacter baumannii (A. baumannii) is an important organism responsible for a variety of nosocomial infections. A. baumannii infections have become problematic worldwide because of the resistance of A. baumannii to multiple antibiotics. Thus, it is clinically significant to explore the relationship between the CRISPR-Cas system and drug resistance in A. baumannii. This study aimed to analyze the genomic characteristics of the A. baumannii strain AB3 containing the type I-Fb CRISPR-Cas system, which was isolated from a tertiary care hospital in China, and to investigate the relationship between the CRISPR-Cas system and antibiotic resistance in this strain. The whole-genome sequencing (WGS) of the AB43 strain was performed using Illumina and PacBio sequencing. The complete genome of AB43 consisted of a 3,854,806 bp chromosome and a 104,309 bp plasmid. The specific characteristics of the CRISPR-Cas system in AB43 are described as follows: (1) The strain AB43 carries a complete type I-Fb CRISPR-Cas system; (2) Homology analysis confirmed that the cas genes in AB43 share high sequence similarity with the same subtype cas genes; (3) A total of 28 of 105 A. baumannii AB43 CRISPR spacers matched genes in the bacteriophage genome database and the plasmid database, implying that the CRISPR-Cas system in AB43 provides immunity against invasive bacteriophage and plasmids; (4) None of the CRISPR spacers in A. baumannii AB43 were matched with antimicrobial resistance genes in the NCBI database. In addition, we analyzed the presence of antibiotic resistance genes and insertion sequences in the AB43 strain and found that the number of antibiotic resistance genes was not lower than in the “no CRISPR-Cas system” strain. This study supports the idea that the CRISPR-Cas system may inhibit drug-resistance gene expression via endogenous gene regulation, except to the published mechanism that the CRISPR-Cas system efficiently limits the acquisition of antibiotic resistance genes that make bacteria sensitive to antibiotics.

Background: Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. The gut microbiome may modify disease risk associated with arsenic exposure. Our aim was to examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)—a surrogate marker for atherosclerosis. Methods: We recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015–2016. 16S rRNA gene sequencing was conducted on microbial DNA extracted from the fecal samples. Arsenic exposure was measured using data on arsenic concentration in drinking water wells over time to derive a time-weighted water arsenic index. Multivariable linear regression models were used to test the inter-relationships between arsenic exposure, relative abundance of selected bacterial taxa from phylum to genus levels, and IMT. Results: We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes, Proteobacteria, and Firmicutes. However, none of the associations retained significance after correction for multiple testing. The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with IMT after correction for multiple testing (P-value = 0.02 and 0.03, respectively). Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-μm (95% CI: 7.8, 28.5) and 97.3-μm (95% CI: 42.3, 152.3) difference in IMT, respectively. These two taxa were also the only selected family and genus using the LASSO variable selection method. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04). Conclusions: Our findings suggest a role of Citrobacter in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure. Keywords: Arsenic exposure, Atherosclerosis, Bangladesh, Cardiovascular disease, Carotid intima-media thickness, Gut microbiome