Influence of humanistic care on negative emotions, nursing quality, and patient satisfaction in outpatient gynecological surgery.

OBJECTIVE: To explore the impact of humanistic care on negative emotions, nursing quality and patient satisfaction among women undergoing outpatient gynecological surgery. METHODS: This retrospective study involved 108 patients who underwent outpatient gynecological surgery at the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between August 2022 and August 2023. The patients were divided into two groups: 51 patients received routine care (control group) and 57 received humanistic care (experimental group). Data collected included vital signs (heart rate [HR] and systolic/diastolic blood pressure [SBP/DBP]), pain levels (Visual Analogue Scale [VAS] scores at 12 and 24 hours postoperative), negative emotions (Self-rating Anxiety/Depression Scale [SAS/SDS]), comfort (Kolcaba's General Comfort Questionnaire [GCQ]), sexual functioning (Brief Index of Sexual Functioning for Women), nursing quality (errors, defects, and complaints) and patient satisfaction. RESULTS: Intraoperative SBP, DBP, along with HR, were significantly lower in the experimental group compared to the control group (all P<0.05). Postoperative pain levels at both 12 and 24 hours were also significantly reduced in the experimental group (both P<0.01). Furthermore, the experimental group demonstrated significant reductions in SAS and SDS scores and higher GCQ scores across physical, psychospiritual, environmental, and sociocultural dimensions (all P<0.05). There were no significant differences between the groups in terms of sexual desire, activity, and satisfaction (all P>0.05). Nursing quality was significantly better (P=0.029) and patient satisfaction with nursing care was higher (P=0.015) in the experimental group. CONCLUSIONS: Humanistic care significantly reduces negative emotions and enhances comfort, nursing quality, and patient satisfaction in women undergoing outpatient gynecological surgery. This approach does not affect sexual functioning indicators but offers substantial improvements in overall patient care and outcomes. Its high value for clinical promotion underscores its potential as a transformative approach in outpatient gynecological settings.

Screening of polyurethane-degrading microbes using a quenching fluorescence probe by microfluidic droplet sorting.

Excessive use of polyurethane (PU) polymers has led contributed to serious environmental pollution. The plastic recycling technology using microorganisms and enzymes as catalysts offers a promising green and low-carbon approach for managing plastic waste. However, current methods for screening PU-degrading strains suffer from drawbacks such as being time-consuming and inefficient. Herein, we present a novel approach for screening PU-degrading microorganisms using a quenching fluorescent probe along with the fluorescence-activated droplet sorting (FADS). The FPAP could specifically recognize the 4,4'-methylenedianiline (MDA) derivates released from PU degradation, with fluorescence quenching as a response. Based on the approach, we successfully screen two PU-degrading strains (Burkholderia sp. W38 and Bacillus sp. C1). After 20 d of cultivation, strain W38 and C1 could degrade 41.58% and 31.45% of polyester-PU film, respectively. Additionally, three metabolites were identified during the degradation of PU monomer (2,4-toluene diamine, 2,4-TDA) and a proposed degradation pathway was established. Consequently, the fluorescence probe integrated with microfluidic droplet systems, demonstrates potential for the development of innovative PU-biocatalysts. Furthermore, the identification of the 2,4-TDA degradation pathway provides valuable insights that can propel advancements in the field of PU biodegradation.

Association between life's essential 8 and testosterone deficiency in US men: findings from national health and nutrition examination survey (NHANES) 2011-2016.

Background: Testosterone deficiency (TD) is closely associated with cardiovascular diseases (CVD). We intended to explore the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of TD among US male adults. Methods: The population-based cross-sectional study selected male adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. According to the American Heart Association definitions, the LE8 score was measured on a scale of 0-100, and divided into health behavior and health factor scores, simultaneously. Furthermore, these scores were categorized into low (0-49), moderate (50-79), and high (80-100) classifications. TD is defined as a total testosterone level below 300ng/dL. Correlations were investigated by weighted multivariable logistic regression, and the robustness of the results were verified by subgroup analysis. Results: A total of 4971 male adults with an average age of 47.46 ± 0.41 years were eligible for the final analyses, of whom 1372 were determined to have TD. The weighted mean LE8 score of the study population was 68.11 ± 0.41. After fully adjusting potential confounders, higher LE8 scores were significantly associated with low risk of TD (odd ratio [OR] for each 10-point increase, 0.79; 95% CI, 0.71-0.88) in a linear dose-response relationship. Similar patterns were also identified in the association of health factor scores with TD (OR for each 10-point increase, 0.74; 95% CI, 0.66-0.83). These results persisted when LE8 and health factor scores was categorized into low, moderate, and high groups. The inversed association of LE8 classifications and TD remained statistically significant among older, obese, and men without CVD. Conclusions: LE8 and its health factor subscales scores were negatively associated with the presence of TD in linear fashions. Promoting adherence to optimal cardiovascular health levels may be advantageous to alleviate the burden of TD.

Knowledge, Attitude and Practice of Radiologists Regarding Artificial Intelligence in Medical Imaging.

Purpose: This study aimed to investigate the knowledge, attitudes, and practice (KAP) of radiologists regarding artificial intelligence (AI) in medical imaging in the southeast of China. Methods: This cross-sectional study was conducted among radiologists in the Jiangsu, Zhejiang, and Fujian regions from October to December 2022. A self-administered questionnaire was used to collect demographic data and assess the KAP of participants towards AI in medical imaging. A structural equation model (SEM) was used to analyze the relationships between KAP. Results: The study included 452 valid questionnaires. The mean knowledge score was 9.01±4.87, the attitude score was 48.96±4.90, and 75.22% of participants actively engaged in AI-related practices. Having a master's degree or above (OR=1.877, P=0.024), 5-10 years of radiology experience (OR=3.481, P=0.010), AI diagnosis-related training (OR=2.915, P<0.001), and engaging in AI diagnosis-related research (OR=3.178, P<0.001) were associated with sufficient knowledge. Participants with a junior college degree (OR=2.139, P=0.028), 5-10 years of radiology experience (OR=2.462, P=0.047), and AI diagnosis-related training (OR=2.264, P<0.001) were associated with a positive attitude. Higher knowledge scores (OR=5.240, P<0.001), an associate senior professional title (OR=4.267, P=0.026), 5-10 years of radiology experience (OR=0.344, P=0.044), utilizing AI diagnosis (OR=3.643, P=0.001), and engaging in AI diagnosis-related research (OR=6.382, P<0.001) were associated with proactive practice. The SEM showed that knowledge had a direct effect on attitude (ß=0.481, P<0.001) and practice (ß=0.412, P<0.001), and attitude had a direct effect on practice (ß=0.135, P<0.001). Conclusion: Radiologists in southeastern China hold a favorable outlook on AI-assisted medical imaging, showing solid understanding and enthusiasm for its adoption, despite half lacking relevant training. There is a need for more AI diagnosis-related training, an efficient standardized AI database for medical imaging, and active promotion of AI-assisted imaging in clinical practice. Further research with larger sample sizes and more regions is necessary.

Intrauterine chromium exposure and cognitive developmental delay: The modifying effect of genetic predisposition.

There is limited evidence on the effects of intrauterine chromium (Cr) exposure on children's cognitive developmental delay (CDD). Further, little is known about the genetic factors in modifying the association between intrauterine Cr exposure and CDD. The present study involved 2361 mother-child pairs, in which maternal plasma Cr concentrations were assessed, a polygenic risk score for the child was constructed, and the child's cognitive development was evaluated using the Bayley Scales of Infant Development. The risks of CDD conferred by intrauterine Cr exposure in children with different genetic backgrounds were evaluated by logistic regression. The additive interaction between intrauterine Cr exposure and genetic factors was evaluated by calculating the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI). According to present study, higher intrauterine Cr exposure was significantly associated with increased CDD risk [each unit increase in ln-transformed maternal plasma Cr concentration (ln-Cr): adjusted OR (95 % CI), 1.18 (1.04-1.35); highest vs lowest quartile: adjusted OR (95 % CI), 1.57 (1.10-2.23)]. The dose-response relationship of intrauterine Cr exposure and CDD for children with high genetic risk was more prominent [each unit increased ln-Cr: adjusted OR (95 % CI), 1.36 (1.09-1.70)]. Joint effects between intrauterine Cr exposure and genetic factors were found. Specifically, for high genetic risk carriers, the association between intrauterine Cr exposure and CDD was more evident [highest vs lowest quartile: adjusted OR (95 % CI), 2.33 (1.43-3.80)]. For those children with high intrauterine Cr exposure and high genetic risk, the adjusted AP was 0.39 (95 % CI, 0.07-0.72). Conclusively, intrauterine Cr exposure was a high-risk factor for CDD in children, particularly for those with high genetic risk. Intrauterine Cr exposure and one's adverse genetic background jointly contribute to an increased risk of CDD in children.

Identification and Validation of New DNA-PKcs Inhibitors through High-Throughput Virtual Screening and Experimental Verification.

DNA-PKcs is a crucial protein target involved in DNA repair and response pathways, with its abnormal activity closely associated with the occurrence and progression of various cancers. In this study, we employed a deep learning-based screening and molecular dynamics (MD) simulation-based pipeline, identifying eight candidates for DNA-PKcs targets. Subsequent experiments revealed the effective inhibition of DNA-PKcs-mediated cell proliferation by three small molecules (5025-0002, M769-1095, and V008-1080). These molecules exhibited anticancer activity with IC50 (inhibitory concentration at 50%) values of 152.6 µM, 30.71 µM, and 74.84 µM, respectively. Notably, V008-1080 enhanced homology-directed repair (HDR) mediated by CRISPR/Cas9 while inhibiting non-homologous end joining (NHEJ) efficiency. Further investigations into the structure-activity relationships unveiled the binding sites and critical interactions between these small molecules and DNA-PKcs. This is the first application of DeepBindGCN_RG in a real drug screening task, and the successful discovery of a novel DNA-PKcs inhibitor demonstrates its efficiency as a core component in the screening pipeline. Moreover, this study provides important insights for exploring novel anticancer therapeutics and advancing the development of gene editing techniques by targeting DNA-PKcs.

Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach.

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005-2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (ß = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

Pressure-Induced Re-Entrant Superconductivity in Transition Metal Dichalcogenide TiSe2.

Transition metal dichalcogenide TiSe2 exhibits a superconducting dome within a low pressure range of 2-4 GPa, which peaks with the maximal transition temperature Tc of ≈1.8 K. Here it is reported that applying high pressure induces a new superconducting state in TiSe2, which starts at ≈16 GPa with a substantially higher Tc that reaches 5.6 K at ≈21.5 GPa with no sign of decline. Combining high-throughput first-principles structure search, X-ray diffraction, and Raman spectroscopy measurements up to 30 GPa, It is found that TiSe2 undergoes a first-order structural transition from the 1T phase under ambient pressure to a new 4O phase under high pressure. Comparative ab initio calculations reveal that while the conventional phonon-mediated pairing mechanism may account for the superconductivity observed in 1T-TiSe2 under low pressure, the electron-phonon coupling of 4O-TiSe2 is too weak to induce a superconducting state whose transition temperature is as high as 5.6 K under high pressure. The new superconducting state found in pressurized TiSe2 requires further study on its underlying mechanism.

Collaborative management of environmental pollution and carbon emissions drives local green growth: An analysis based on spatial effects.

Collaborative management of environmental pollution and carbon emissions (CMPC) has been a major policy instrument to promote Sustainable Development Goals (SDG) in recent years. However, the relationship between the benefits and drawbacks of this environmental management practice for green growth in and around a local area remains to be clarified. Using 30 provinces in China during 2001-2019 as the object of analysis, we assessed the efficiency of local CMPC practices using the nonradial directional distance function (NDDF) model, predicted local green growth using the frontier green complexity index (GCI), and empirically examined the spatial effects, locational heterogeneity, and threshold characteristics of the relationship using the spatial Durbin model and the panel threshold model. Our study finds that although efficient CMPC does drive local green growth, the promotion effect is nonlinear with decreasing marginal effect. This effect is particularly obvious in economically developed regions with higher CMPCs, which will absorb resources from neighboring regions and create a "siphoning" effect. It was found that local financial support and foreign direct investment (FDI) can radiate green growth to neighboring regions; therefore, CMPC practice needs to pay more attention to the effect of joint governance, supplemented by financial and foreign investment policy tools, to better promote the green transformation of local economy.

Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma.

BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC. AIM: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment. METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry. RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC. CONCLUSION: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Prenatal EDC exposure, DNA Methylation, and early childhood growth: A prospective birth cohort study.

BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. OBJECTIVE: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). METHOD: This study included 285 mother-child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. RESULTS: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P < 0.05). CONCLUSION: Our results revealed that prenatal exposure to EDCs was associated with a higher risk of childhood obesity, with specific DNAm acting as a partial mediator.

Van Hove annihilation and nematic instability on a kagome lattice.

A nematic phase breaks the point-group symmetry of the crystal lattice and is known to emerge in correlated materials. Here we report the observation of an intra-unit-cell nematic order and associated Fermi surface deformation in the kagome metal ScV6Sn6. Using scanning tunnelling microscopy and scanning tunnelling spectroscopy, we reveal a stripe-like nematic order breaking the crystal rotational symmetry within the kagome lattice itself. Moreover, we identify a set of Van Hove singularities adhering to the kagome-layer electrons, which appear along one direction of the Brillouin zone and are annihilated along other high-symmetry directions, revealing rotational symmetry breaking. Via detailed spectroscopic maps, we further observe an elliptical deformation of the Fermi surface, which provides direct evidence for an electronically mediated nematic order. Our work not only bridges the gap between electronic nematicity and kagome physics but also sheds light on the potential mechanism for realizing symmetry-broken phases in correlated electron systems.

Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties. RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level. CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

A Review: Visuospatial Dysfunction in Patients with the Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) impairs visuospatial function, and this is one of the most obvious areas of cognitive impairment in CSVD. So, recognizing, monitoring, and treating visuospatial dysfunction are all important to the prognosis of CSVD. This review discussed the anatomical and pathological mechanisms, clinical recognition (scales, imaging, and biomarkers), and treatment of cognitive impairment especially visuospatial dysfunction in CSVD.

miR-4443 Contained Extracellular Vesicles: A Factor for Endometriosis Progression by PI3K/AKT/ACSS2 Cascade in-vitro.

Introduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM. Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients. Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P<0.0001) and dysmenorrhea (r=0.42; P<0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624-0.858; P<0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880-0.978; P<0.05) for the combination of miR-4443 and dysmenorrhea. Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence.

Unlocking nature's secrets: The pivotal role of WRKY transcription factors in plant flowering and fruit development.

The WRKY transcription factor family is a key player in the regulatory mechanisms of flowering plants, significantly influencing both their biotic and abiotic response systems as well as being vital to numerous physiological and biological functions. Over the past two decades, the functionality of WRKY proteins has been the subject of extensive research in over 50 plant species, with a strong focus on their roles in responding to various stresses. Despite this extensive research, there remains a notable gap in comprehensive studies aimed at understanding how specific WRKY genes directly influence the timing of flowering and fruit development. This review offers an up-to-date look at WRKY family genes and provides insights into the key genes of WRKY to control flowering, enhance fruit ripening and secondary metabolism synthesis, and maintain fruit quality of various plants, including annuals, perennials, medicinal, and crop plants. The WRKY transcription factors serve as critical regulators within the transcriptional regulatory network, playing a crucial role in the precise enhancement of flowering processes. It is also involved in the up-regulation of fruit ripening was strongly demonstrated by combined transcriptomics and metabolomic investigation. Therefore, we speculated that the WRKY family is known to be a key regulator of flowering and fruiting in plants. This detailed insight will enable the identification of the series of molecular occurrences featuring WRKY proteins throughout the stages of flowering and fruiting.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.