Transcription factor NtMYB59 targets NtMYB12 to negatively regulate the biosynthesis of polyphenols in Nicotiana tabacum.

MYB12 is a key regulator that has been shown to promote the accumulation of various phenylpropanoid compounds in plants. However, the regulation of MYB12 gene is largely unknown. In this study, we found that overexpression of the NtMYB59 gene significantly inhibited the accumulation of chlorogenic acid (CGA), flavonols, and anthocyanins in tobacco, while knock-down and knock-out of NtMYB59 significantly increased the contents of these polyphenol compounds. Transcriptome analysis between WT and NtMYB59-OE plants revealed several differentially expressed genes (DEGs) encoding crucial enzymes in the phenylpropanoid pathway and the transcription factor NtMYB12. ChIP-seq assay further indicated that NtMYB12 might be a direct target of NtMYB59. Subsequent yeast one-hybrid, electrophoretic mobility shift assay, and Dual-Luciferase assays confirmed that NtMYB59 directly binds to the promoter of NtMYB12 to inhibit its expression. Moreover, loss-function of NtMYB59 significantly promoted the accumulation of flavonols and anthocyanins in ntmyb59, but their contents in ntmyb59/ntmyb12 double mutants were significantly lower than that of WT and ntmyb59 plants, indicating that the regulation of NtMYB59 on flavonoids biosynthesis depends on the activity of NtMYB12. Our study revealed that NtMYB59 regulates the expression of NtMYB12, and provided new potential strategies for modulating phenylpropanoids biosynthesis in tobacco.

Targeted Therapies in Pancreatic Cancer: A New Era of Precision Medicine.

Pancreatic ductal adenocarcinoma (PDAC), a leading cause of cancer mortality in the United States, presents significant treatment challenges due to its late diagnosis and poor prognosis. Despite advances, the five-year survival rates remain dismally low, with only a fraction of patients eligible for potentially curative surgical interventions. This review aims to comprehensively examine the current landscape of targeted therapies in PDAC, focusing on recent developments in precision medicine approaches. We explore various molecular targets, including KRAS mutations, DNA damage repair deficiencies, mismatch repair pathway alterations, and rare genetic fusions. The review discusses emerging therapies, such as PARP inhibitors, immune checkpoint inhibitors, and novel targeted agents, like RET and NTRK inhibitors. We analyze the results of key clinical trials and highlight the potential of these targeted approaches in specific patient subgroups. Recent developments in PDAC research have emphasized precision oncology, facilitated by next-generation sequencing and the identification of genetic and epigenetic alterations. This approach tailors treatments to individual genetic profiles, improving outcomes and reducing side effects. Significant strides have been made in classifying PDAC into various subtypes, enhancing therapeutic precision. The identification of specific mutations in genes like KRAS, along with advancements in targeted therapies, including small molecule inhibitors, offers new hope. Furthermore, emerging therapies targeting DNA repair pathways and immunotherapeutic strategies also show promising results. As research evolves, integrating these targeted therapies with conventional treatments might improve survival rates and quality of life for PDAC patients, underscoring the shift towards a more personalized treatment paradigm.

Analysis of the Incidence and Factors Influencing Medication Administration Errors Among Nurses: A Retrospective Study.

AIMS: To explore the incidence and factors influencing medication administration errors (MAEs) among nurses. BACKGROUND: Medication administration is a global concern for patient safety. Few studies have assessed the incidence of MAEs or explored factors that considered the interplay between behaviour, the individual and the environment. METHODS: This retrospective study included 342 MAEs reported in the electronic nursing adverse event reporting system between January 2019 and September 2023 at a university-affiliated teaching hospital in China. Data on nurses' demographics and medication administration were extracted from the nursing adverse event reports. The reports were classified according to the severity of patient harm. The causes of the 342 MAEs were retrospectively analysed using content analysis based on Bandura's social cognitive theory. Descriptive statistics were used to calculate the proportion of medication errors and the distribution of subcategories. RESULTS: In total, 74.3% of MAEs were adverse events owing to mistakes and resulted in no harm or only minor consequences for patients. Nurses aged 26-35 years and those with 6-10 years of experience were the most common groups experiencing MAEs. Factors influencing MAEs included personal ('knowledge and skills' and 'physical state'), environmental ('equipment and infrastructure,' 'work settings' and 'workload and workflow') and behavioural ('task performance' and 'supervision and communication') factors. The study further highlighted the interrelationships among personal, behavioural and environmental factors. CONCLUSION: Multiple factors influence MAEs among nurses. Nurse-related MAEs and the relationship between behaviours, individual factors and the environment, as well as ways to reduce the occurrence of MAEs, should be considered in depth. RELEVANCE TO CLINICAL PRACTICE: Understanding the factors influencing MAEs can inform training programs and improve the clinical judgement of healthcare professionals involved in medication administration, ultimately improving patient prognoses and reducing MAEs. PATIENT OR PUBLIC CONTRIBUTION: The findings can help develop clinical guidelines for preventing MAEs.

Synergistic release of Cd(II) and As(V) from ternary sorption systems containing ferrihydrite nanoparticles: The role of binary and ternary surface complexes.

Cadmium (Cd) and arsenic (As) generally exhibit mutually beneficial co-sorption behavior on iron oxyhydroxides through multiple mechanisms, including surface precipitation, ternary surface complexes, and electrostatic interactions. However, the numerous factors that control the immobilization of Cd and As in turn complicated the processes and mechanisms involved in their co-desorption from iron minerals, which hindered the full understanding of their geochemical behaviors. Here, the simultaneous release of Cd(II) and As(V) from newly precipitated ferrihydrite nanoparticles by either Ca or P was investigated through kinetics and isothermal desorption experiments. We showed that the Cd(II) and As(V) present two-phase desorption processes (rapid desorption and slow desorption) in both binary (Fe-Cd or Fe-As alone) and ternary systems (Fe-Cd-As co-presence). Compared to their binary counterparts, Cd(II) and As(V) in the ternary systems are more prone to detachment from ferrihydrite. Further desorption of Cd(II) and As(V) at different co-presence scenarios (different initial concentrations) demonstrated mutual promotion behaviour towards their counterparts; the co-presence of Cd(II) facilitates the desorption of As(V), while the co-presence of As(V) also promotes the desorption of Cd(II). XPS and FTIR results demonstrated that either Ca or P showed minor effects on the binding environment of Cd and As. Further results from the in-situ ATR-FTIR experiment and second derivative peak fitting analysis indicate that the enhanced detachment of Cd(II) and As(V) from the ternary system may be due to the synergistic desorption of the ternary surface complexes and other surface complex species. Our results provide new insights into the prediction of the environmental behaviour of the coexistence of Cd(II) and As(V) in iron-rich geological settings. The potential environmental risks of iron-based remediation methods should be considered due to the enhanced bioavailability of Cd(II) and As(V) in co-presence circumstances.

Association between alcohol consumption and incidence of dementia in current drinkers: linear and non-linear mendelian randomization analysis.

Background: Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers. Methods: This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe. Findings: 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship (p = 0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk. Interpretation: This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia. Funding: The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

Incidence and risk factors of neonatal peripherally inserted central catheter-related thrombosis: A systematic review and meta-analysis.

BACKGROUND: Catheter-related thrombosis is a common complication of the peripherally inserted central catheter (PICC) in neonates, leading to unintended tube removal and significantly affecting neonatal health and safety. Despite widespread reporting on the estimated occurrence and factors contributing to neonatal PICC-related thrombosis, these findings have not been synthesized. OBJECTIVES: The purpose of this study was to determine the incidence and risk factors of neonatal PICC-related thrombosis. DESIGN: Systematic literature review and meta-analysis. METHODS: Two independent researchers systematically explored multiple databases-such as PubMed, Medline, Embase and the Cochrane Library-from their inception until October 2023. Our study aggregates and scrutinizes studies specifically addressing the incidence and risk factors of neonatal PICC-related thrombosis. Employing the RevMan 5.3 software, a meta-analysis was executed to determine the incidence of both thrombosis and odds ratios (OR), accompanied by their respective 95% confidence intervals (CI) for the risk factors. RESULTS: A total of 327 articles were screened, and data from 24 studies were used in synthesis. Neonatal PICC-related thrombosis incidence varied from 0.23% to 17.91%. The pooled incidence was 2% (95% CI: 1%-2%; I2 = 94%; p < .0001). The study identified 12 risk factors, including insertion sites in the lower extremities (OR = 0.22; 95% CI: 0.09-0.56; p = .001), gestational age <28 weeks, abdominal pathology, fresh frozen plasma by day 5 > 50 mL/kg, PICC tip location (proximal placement), two lumens, three lumens, prolonged hospital stay, infection, mothers' use of anticoagulants, patients with cardiac insufficiency and being twin-to-twin transfusion syndrome donor. CONCLUSIONS: The analysis indicates an overall pooled incidence of neonatal PICC-related thrombosis of 2%. Twelve factors were identified as risks associated with neonatal PICC-related thrombosis. Understanding the risk factors can provide evidence-based recommendations for improving awareness, control and treatment and better nursing management. RELEVANCE TO CLINICAL PRACTICE: This systematic review and meta-analysis illuminates the incidence and risk factors linked to neonatal PICC-related thrombosis, delivering essential insights pivotal for clinical decision-making and enhancing patient care within neonatal health care settings.

Extracellular vesicles from alveolar macrophages harboring phagocytosed methicillin-resistant Staphylococcus aureus induce necroptosis.

Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

NtWIN1 regulates the biosynthesis of scopoletin and chlorogenic acid by targeting NtF6'H1 and NtCCoAMT genes in Nicotiana tabacum.

Scopoletin and chlorogenic acid (CGA) are important polyphenols that regulate plant growth, development, and stress resistance. The ERF transcription factor WAX INDUCER1 (WIN1) promotes the biosynthesis of cutin, suberine, and wax. However, its full roles in regulating the accumulation of plant secondary metabolites still remain to be further clarified. In this study, NtWIN1 gene encoding a SHINE-type AP2/ERF transcription factor of the Va subgroup was identified from N. tabacum. NtWIN1 showed high expression levels in tobacco stems, sepals, and pistils. Overexpression (OE) and knock-out of NtWIN1 showed that it promoted the accumulation of total polyphenols and altered their composition. Compare to that of WT plants, the CGA contents significantly increased by 25%-50% in the leaves, flowers, and capsules of OE lines, while the scopoletin contents in the OE plants significantly decreased by 30%-67%. In contrast, the CGA contents in ntwin1 lines reduced by 23%-26%, and the scopoletin contents in ntwin1 increased by 38%-75% compare to that of WT plants. Chromatin immunoprecipitation and Dual-Luc transcription activation assays showed that NtWIN1 could bind to the promoters of NtF6'H1 and NtCCoAMT, thereby modulating their expression. The scopoletin content in ntwin1/ntf6'h1 double mutant was significantly lower than that in ntwin1 and WT plants, but showed no significant differences with that in ntf6'h1 mutant, further indicating that the inhibition of NtWIN1 on scopoletin accumulation depends on the activity of NtF6'H1. Our study illustrates the new roles of NtWIN1, and provides a possible target for regulating the synthesis of polyphenols in tobacco.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study.

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

MpANT regulates meristem development in Marchantia polymorpha.

Meristems are crucial for organ formation, but our knowledge of their molecular evolution is limited. Here, we show that AINTEGUMENTA (MpANT) in the euANT branch of the APETALA2-like transcription factor family is essential for meristem development in the nonvascular plant Marchantia polymorpha. MpANT is expressed in the thallus meristem. Mpant mutants show defects to maintain meristem identity and undergo meristem duplication, while MpANT overexpressers show ectopic thallus growth. MpANT directly upregulates MpGRAS9 in the SHORT-ROOT (SHR) branch of the GRAS family. In the vascular plant Arabidopsis thaliana, the euANT-branch genes PLETHORAs (AtPLTs) and AtANT are involved in the formation and maintenance of root/shoot apical meristems and lateral organ primordia, and AtPLTs directly target SHR-branch genes. In addition, euANTs bind through a similar DNA-binding motif to many conserved homologous genes in M. polymorpha and A. thaliana. Overall, the euANT pathway has an evolutionarily conserved role in meristem development.

Enhancement of colour formation of fermented sausages by overexpression of nitric oxide synthase in Staphylococcus vitulinus under hydrogen peroxide stress.

This study used hydrogen peroxide (H2O2) treatment to overexpress the gene of nitric oxide synthase (nos) in Staphylococcus vitulinus, which was then inoculated into fermented sausages to observe its effect on colour development. The results showed that a low concentration of H2O2 (50 mM) could up-regulate the expression of nos by increasing the oxidative stress level of S. vitulinus. At 2 h after treatment, the expression of nos in S. vitulinus was the highest (P < 0.05), and the relative enzyme activity was increased to about 1.5 times that of the untreated. The growth of S. vitulinus was not substantially affected by 50-mM H2O2 treatment (P > 0.05). When H2O2-treated S. vitulinus was inoculated into fermented sausages, the content of nitrosomyoglobin was increased, and the a*-value (indicating redness) was not significantly different from that in the group treated with nitrite (P > 0.05). This study provides a potential method to enhance the ability of S. vitulinus for colourising fermented sausage by inducing the overexpression of nos.

Engineered Antibodies as Cancer Radiotheranostics.

Radiotheranostics is a rapidly growing approach in personalized medicine, merging diagnostic imaging and targeted radiotherapy to allow for the precise detection and treatment of diseases, notably cancer. Radiolabeled antibodies have become indispensable tools in the field of cancer theranostics due to their high specificity and affinity for cancer-associated antigens, which allows for accurate targeting with minimal impact on surrounding healthy tissues, enhancing therapeutic efficacy while reducing side effects, immune-modulating ability, and versatility and flexibility in engineering and conjugation. However, there are inherent limitations in using antibodies as a platform for radiopharmaceuticals due to their natural activities within the immune system, large size preventing effective tumor penetration, and relatively long half-life with concerns for prolonged radioactivity exposure. Antibody engineering can solve these challenges while preserving the many advantages of the immunoglobulin framework. In this review, the goal is to give a general overview of antibody engineering and design for tumor radiotheranostics. Particularly, the four ways that antibody engineering is applied to enhance radioimmunoconjugates: pharmacokinetics optimization, site-specific bioconjugation, modulation of Fc interactions, and bispecific construct creation are discussed. The radionuclide choices for designed antibody radionuclide conjugates and conjugation techniques and future directions for antibody radionuclide conjugate innovation and advancement are also discussed.

RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.

Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

BACKGROUND: Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC. METHODS: This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC. RESULTS: Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy. CONCLUSIONS: We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.

Obesity correlates with the immunosuppressive ILC2s-MDSCs axis in advanced breast cancer.

AIM: We investigated the relationship between the group 2 innate lymphoid cells (ILC2s)-myeloid-derived suppressor cells (MDSCs) axis and obesity-related breast cancer. METHODS: Fifty-eight patients with breast cancer who had first relapse and metastasis between January 2019 and August 2021 were enrolled. The proportions of ILC2s and MDSCs in blood and the levels of cytokines in serum were detected with flow cytometry. Correlation analysis among clinical characteristics (such as body mass index [BMI]), cytokines, ILC2s, and MDSCs was conducted. RESULTS: There was a significant difference in the proportions of ILC2s and MDSCs between the high BMI group and the normal BMI group (p < .05). In the triple-negative breast cancer (TNBC) patients, the proportions of ILC2s and MDSCs in the obese group were significantly higher than those in the nonobese group (p < .05). In all breast cancer patients, there was a positive correlation between BMI and the ILC2s-MDSCs axis (p < .05). However, there was no correlation observed between the number of metastases, progression-free survival, and the ILC2s-MDSCs axis (p > .05). Additionally, ILC2s showed positive correlations with MDSCs, interleukin-5 (IL-5), IL-10, IL-17A, (PD-L1), programmed cell death 2 ligand 2 (PD-L2), and molecular typing (p < .05). Similarly, MDSCs exhibited positive correlations with IL-5, IL-8, IL-9, IL-17A, PD-L1, and PD-L2 (p < .05). In patients with TNBC, there was a positive correlation between BMI and IL-5 (p < .05). CONCLUSION: Conclusively, obesity may enhance the immunosuppressive effect of the ILC2-MDSC axis in advanced breast cancer. IL-5 may play a vital role in the ILC2-MDSC axis and obesity in TNBC.

Therapeutic robots for post-stroke rehabilitation.

Stroke is a prevalent, severe, and disabling health-care issue on a global scale, inevitably leading to motor and cognitive deficits. It has become one of the most significant challenges in China, resulting in substantial social and economic burdens. In addition to the medication and surgical interventions during the acute phase, rehabilitation treatment plays a crucial role in stroke care. Robotic technology takes distinct advantages over traditional physical therapy, occupational therapy, and speech therapy, and is increasingly gaining popularity in post-stroke rehabilitation. The use of rehabilitation robots not only alleviates the workload of healthcare professionals but also enhances the prognosis for specific stroke patients. This review presents a concise overview of the application of therapeutic robots in post-stroke rehabilitation, with particular emphasis on the recovery of motor and cognitive function.

POLQ identifies a better response subset to immunotherapy in muscle-invasive bladder cancer with high PD-L1.

BACKGROUND: Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. METHODS: A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo-cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC-108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. RESULTS: We identified POLQhigh PD-L1high patients could benefit more from immunotherapy and platinum-based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. CONCLUSIONS: The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD-L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.

TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma.

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co-occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild-type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Status and related factors of professional growth among young nursing talents: a cross-sectional study in China.

BACKGROUND: The shortage of nurses has been a global human resources problem. A good professional growth environment is essential to developing potential nursing students and attracting nurses to join, and it has great significance in reducing nurse turnover. However, nurses' comprehensive perceptions of professional growth have not yet been examined. METHODS: A cluster sampling method was used to conduct a professional growth questionnaire survey on young nursing talents from a large Chinese public tertiary A hospital in March 2022. RESULTS: The score of professional growth among 243 young nursing talents was 57.92 ± 9.607, with a scoring rate of 77.23%. The scores for dimensions of professional growth, from lowest to highest, were rehabilitation growth, promotion speed, professional goal progress, and professional ability development. Attitudes towards participating in training, service as the quality manager or clinical teacher, self-efficacy, professional title, work-family support, education, and organizational commitment of young nursing talents were significantly associated with professional growth. CONCLUSION: The professional growth of young nursing talents was at a moderate level and needed to be strengthened. Nursing leaders and managers are expected to develop management practices to enhance young nursing talents' professional growth in combination with the related factors.