The introgression of BjMYB113 from Brassica juncea leads to purple leaf trait in Brassica napus.

The purple leaves of Brassica napus are abundant in anthocyanins, which are renowned for their role in conferring distinct colors, stress tolerance, and health benefits, however the genetic basis of this trait in B. napus remains largely unelucidated. Herein, the purple leaf B. napus (PL) exhibited purple pigments in the upper epidermis and a substantial increase in anthocyanin accumulation, particularly of cyanidin, compared to green leaf B. napus (GL). The genetic control of the purple leaf trait was attributed to a semi-dominant gene, pl, which was mapped to the end of chromosome A03. However, sequencing of the fragments amplified by the markers linked to pl indicated that they were all mapped to chromosome B05 from B. juncea. Within this B05 chromosomal segment, the BjMYB113 gene-specific marker showed perfect co-segregation with the purple leaf trait in the F2 population, suggesting that the BjMYB113 introgression from B. juncea was the candidate gene for the purple leaf trait in B. napus. To further verify the function of candidate gene, CRISPR/Cas9 was performed to knock out the BjMYB113 gene in PL. The three myb113 mutants exhibited evident green leaf phenotype, absence of purple pigments in the adaxial epidermis, and a significantly reduced accumulation of anthocyanin compared to PL. Additionally, the genes involved in positive regulatory (TT8), late anthocyanin biosynthesis (DFR, ANS, UFGT), as well as transport genes (TT19) were significantly suppressed in the myb113 mutants, further confirming that BjMYB113 was response for the anthocyanin accumulation in purple leaf B. napus. This study contributes to an advanced understanding of the regulation mechanism of anthocyanin accumulation in B. napus.

Effect of Parent-Initiated Support on Career Calling Among Chinese Kindergarten Teachers: Basic Psychological Need Satisfaction as Mediator.

Purpose: Possessing a calling to teach is a core and essential quality of good kindergarten teachers, and it is critical to explore which factors positively impact kindergarten teachers' career calling. Developing a career calling is a meaning-making process that can be influenced by the actions of others in the workplace. During the frequent parent-teacher interactions, parent-initiated support may serve as significant interpersonal cues for kindergarten teachers in developing their career calling. Thus, the present study examined the effect of parent-initiated support on kindergarten teachers' career calling. Further, we investigated the multiple mediating roles of global and specific basic psychological need satisfaction based on the self-determination theory (SDT). Methods: Cross-sectional data were collected from 629 kindergarten teachers in China and analyzed using Mplus 8.3 software and the Process 3.5 macro of SPSS 26.0 software. Before testing the hypothesis, we used Mplus 8.3 to save factor scores from the Bifactor model of basic psychological need satisfaction and two uni-dimensional models of parent-initiated support and career calling. Subsequently, using the Process 3.5 macro within SPSS 26.0 software, we conducted path analysis to examine the total and mediating effects between parent-initiated support and kindergarten teachers' career calling. Results: The results revealed a positive effect of parent-initiated support on teachers' career calling. Teachers' global and specific competence need satisfaction partially mediated this positive effect, while the mediating effects of teachers' specific autonomy and relatedness need satisfaction were non-significant. Conclusion: These findings suggest that parent-initiated support is an important job resource for kindergarten teachers' development of career calling. In addition to satisfying global psychological needs, satisfying specific needs (eg, competence need) provides additional benefits to kindergarten teachers' experience of career calling.

Servant leadership and employee voice behavior: the role of employee work reflection and employee proactive personality.

Despite the recent proliferation of scholarly investigations on servant leadership, clarity remains elusive regarding the specific mechanisms and conditions underpinning employee cognitive processes and their responses to servant leadership. Drawing upon social cognitive theory, proposes a moderated mediation model tested through a time-lagged field data from 489 employees in Study 1 and an experimental data in Study 2. We found that servant leadership indirectly enhances employee voice behavior through increased employee work reflection. Additionally, we considered employee proactive personality as a boundary condition for the positive effect of servant leadership. Our results show that servant leadership prompts employee work reflection only when the level of employee proactive personality is high, which in turn increases employee voice behavior. This study presents significant theoretical and practical implications through the integration of social cognitive theory with servant leadership research.

Sitting Time, Physical Activity and Mortality: A Cohort Study In Low-Income Older Americans.

INTRODUCTION: Physical inactivity and sedentary behavior are recognized as independent risk factors for many diseases. However, studies investigating their associations with total and cause-specific mortality in low-income and Black populations are limited, particularly among older adults. METHODS: A prospective cohort study was conducted among 8,337 predominantly low-income and Black Americans aged ≥65 years residing in the southern United States. Participants reported their daily sitting time and leisure-time physical activity (LTPA) at baseline (2002-2009), and mortality data were collected through 2019. Analysis was conducted from September 2022 to October 2023. RESULTS: During a median follow-up of 12.25 years, nearly 50% (n=4,111) were deceased. A prolonged sitting time (>10 hours/day versus <4 hours/day) was associated with elevated all-cause mortality (hazard ratios [HR], 1.15; 95% confidence intervals [CI], 1.04-1.27) after adjusting for LTPA and other potential confounders. LTPA was associated with a reduced risk of all-cause mortality, with an adjusted HR of 0.75 (95% CI 0.64, 0.88) associated with 150-300 minutes per week of moderate-intensity physical activity. Individuals who were physically inactive and had a sitting time of >10 hours/day had the highest mortality risk (HR, 1.48; 95% CI, 1.23-1.78), compared with those who were physically active and had low sitting time. These associations were more pronounced for mortality due to cardiovascular diseases. CONCLUSIONS: High sitting time is an independent risk factor for all-cause and cardiovascular disease mortality, and LTPA could partially attenuate the adverse association of prolonged sitting time with mortality.

Health Care Provider Clustering Using Fusion Penalty in Quasi-Likelihood.

There has been growing research interest in developing methodology to evaluate the health care providers' performance with respect to a patient outcome. Random and fixed effects models are traditionally used for such a purpose. We propose a new method, using a fusion penalty to cluster health care providers based on quasi-likelihood. Without any priori knowledge of grouping information, our method provides a desirable data-driven approach for automatically clustering health care providers into different groups based on their performance. Further, the quasi-likelihood is more flexible and robust than the regular likelihood in that no distributional assumption is needed. An efficient alternating direction method of multipliers algorithm is developed to implement the proposed method. We show that the proposed method enjoys the oracle properties; namely, it performs as well as if the true group structure were known in advance. The consistency and asymptotic normality of the estimators are established. Simulation studies and analysis of the national kidney transplant registry data demonstrate the utility and validity of our method.

Associations of occupational exposure to micro-LiNiCoMnO2 particles with systemic inflammation and cardiac dysfunction in cathode material production for lithium batteries.

Micro-LiNiCoMnO2 (MNCM), a cathode material with highest market share, has increasing demand with the growth of lithium battery industry. However, whether MNCM exposure brings adverse effects to workers remains unclear. This study aimed to explore the association between MNCM exposure with systemic inflammation and cardiac function. A cross-sectional study of 347 workers was undertaken from the MNCM production industry in Guangdong province, China in 2020. Metals in urine were measured using ICP-MS. The associations between metals, systemic inflammation, and cardiac function were appraised using a linear or logistic regression model. Bayesian kernel machine regression (BKMR) and generalized weighted quantile sum (gWQS) models were used to explore mixed metal exposures. The analysis of interaction and mediation was adopted to assess the role of inflammation in the relation between urinary metals and cardiac function. We observed that the levels of lithium (Li) and cobalt (Co) were positively associated with systemic inflammation and heart rate. The amount of Co contributed the highest weight on the increased systemic immune-inflammation index (SII) (59.8%), the system inflammation response index (SIRI) (44.3%), and heart rate (65.0%). Based on the mediation analysis, we estimated that SII mediated 32.3% and 20.9% of the associations between Li and Co with heart rate, and SIRI mediated 44.6% and 22.2% of the associations between Li and Co with heart rate, respectively. This study demonstrated for the first time that MNCM exposure increased the risk of workers' systemic inflammation and elevated heart rate, which were contributed by the excessive Li and Co exposure. Additionally, it indicates that systemic inflammation was a major mediator of the associations of Li and Co with cardiac function in MNCM production workers.

Clinicopathological and immune characterization of mismatch repair deficient endocervical adenocarcinoma.

Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.

Tongue Acupuncture to Treat Dysphagia in Patients with Parkinson's Disease: A Randomized Controlled Trial.

Objective: Parkinson's disease (PD) is a chronic degenerative disease that lacks specific treatment. The incidence of dysphagia in patients with PD is 35%-82%. Dysphagia not only affects nutritional intake but also leads to pneumonia, even asphyxia. This study explored the efficacy of tongue acupuncture for treating dysphagia in patients with PD. Materials and Methods: From March 2021 to June 2023, 64 patients with PD-related dysphagia were chosen from Qingdao Central Hospital and the Affiliated Hospital of Qingdao Binhai University, both in Qindao, Shandong, China. The patients were divided into a tongue acupuncture group (n = 32) and a control group (n = 32). The control group was treated with a VitalStim® 5900 Swallowing Disorder Therapeutic Instrument (CA, USA), and the tongue acupuncture group had tongue acupuncture at Juquan (Ex-HN-10) and Haiquan (Ex-HN-11). Swallowing function and nutritional conditions were compared between the 2 groups after all treatments. Results: The total clinical effective rate in the tongue acupuncture group was higher than that of the control group (P < 0.05). The proportion of grade 1 and grade 2 of the 5-scaled Kubota drinking-water test in the tongue acupuncture group was significantly higher than that in the control group (78.13 % versus 31.26 %; P < 0.05), and the proportion of grade 3, grade 4, and grade 5 was significantly lower than that in the control group (21.87 % versus 68.74 %; P < 0.05). After tongue acupuncture, levels of body mass index, upper-arm circumference, triceps skinfold thickness, hemoglobin, serum albumin, and prealbumin were significantly higher than those in the control group (P < 0.05) and the incidence of complications caused by PD was significantly lower than that in the control group (P < 0.05). Conclusions: Treatment of dysphagia in PD by tongue acupuncture significantly improved swallowing function and nutritional level, and decreased the incidence of complications.

Evaluation of the prevalence of adolescent scoliosis and its associated factors in Gansu Province, China: a cross-sectional study.

Introduction: Gansu Province is situated in the northwest region of China, characterized by diverse and complex topography and a rich diversity of ethnic groups. This study aims to explore the prevalence and risk factors of adolescent suspected scoliosis in Gansu Province through a cross-sectional population study. Methods: From April 2022 to July 2022, a prospective cross-sectional study was conducted in Baiyin City, Jinchang City, Lanzhou City, Linxia Hui Autonomous Prefecture, and Gannan Tibetan Autonomous Prefecture in Gansu Province. The screening covered 3,118 middle and high school students across 24 institutions, including middle and high schools. Diagnosis of suspected scoliosis was established through visual inspection, the Adams forward bend test, and measurement of trunk rotation angle. Employing a custom-designed questionnaire, demographic data were collected, and the prevalence of suspected scoliosis was calculated. Univariate and multivariate logistic regression analyses were employed to assess factors associated with suspected scoliosis. Results: A total of 3,044 participants were ultimately included in the analysis. The overall prevalence of suspected scoliosis was 5.68% in Gansu Province. The peak prevalence for boy is at 14 years (6.70%), while for girl, it is at 15 years (8.75%). Lanzhou City exhibits the highest prevalence rates (boy, 9.82%; girl, 10.16). The results of univariate logistic regression analysis presented that BMI (OR = 0.92, 95% CI: 0.88-0.96), altitude of habitation (1,600 m-2000 m) (OR = 0.50, 95% CI: 0.34-0.73), altitude of habitation (2000 m-3321 m) (OR = 0.58, 95% CI: 0.40-0.83), family medical history (OR = 1.56, 95% CI: 1.02-2.31), and shoulders of unequal height (OR = 1.49, 95% CI: 1.09-2.03) were significantly correlated with suspected scoliosis. The multivariate logistic regression analysis indicated that BMI (OR = 0.91, 95% CI: 0.86-0.95), altitude of habitation (1,600 m-2000 m) (OR = 0.35, 95% CI: 0.23-0.54), altitude of habitation (2000 m-3321 m) (OR = 0.39, 95% CI: 0.24-0.60), family medical history (OR = 1.66, 95% CI:1.08-2.49), and shoulders of unequal height (OR = 1.45, 95% CI:1.06-1.99) were independently associated with suspected scoliosis. Conclusion: Low BMI, residence at an altitude of 1,600 m-3321 m, family medical history, and shoulders of unequal height were independently associated with an increased prevalence of suspected scoliosis. It is recommended to promptly screen high-risk adolescents for suspected scoliosis, provide effective preventive and intervention measures.

Taxonomic revision of two species in the genus Ptychorhynchus Simpson, 1900 (Bivalvia: Unionidae: Gonideinae), with description of a new species.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Cross-sectional study on the impact of cardiac and hepatic iron overload, as measured by MRI T2*, on the quality of life in children with severe beta-thalassemia major.

A cross-sectional study to explore the correlation between cardiac and hepatic iron overload and its impact on the quality of life in children diagnosed with severe beta-thalassemia major (ß-TM). A cohort of 55 pediatric patients with ß-TM, diagnosed via genetic testing at the Affiliated Hospital of Guangdong Medical University from January 2015 to January 2022, was included in this study. The assessment of cardiac and hepatic iron overload was conducted using the magnetic resonance imaging T2* technique. The Chinese version of the Pediatric Quality of Life Inventory (PedsQL) 4.0. Pearson correlation analysis was utilized to assess the relationships between the cardiac and hepatic T2* values and between these T2* values and the total scores of PedsQL 4.0. Analysis showed no significant correlation between cardiac and hepatic T2* values. However, a significant relationship was observed between cardiac T2* values and PedsQL 4.0 total scores (r = 0.313, P < .05), indicating that cardiac, but not hepatic, iron overload is associated with the quality of life. This study highlights the absence of correlation between cardiac and hepatic iron overload levels and demonstrates a significant impact of cardiac iron overload on the quality of life in children with ß-TM. These findings suggest the need for a focused approach to cardiac health in managing ß-TM.

Screening and Anti-angiogenesis Activity of Chiloscyllium plagiosum Anti-human VEGFR2 Single-domain Antibody.

Recently, the incidence of malignant tumors is on the rise and searching for new treatments on it has become the research priority. Blocking the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is one of the treatment strategies that used in the development of specific anti-angiogenic drugs. The deficiencies in tissue penetration and affinity maturation become the weakness of these drugs in anti-tumors applications. The single heavy chain antibody found in Chiloscyllium plagiosum, which has a low molecular weight and superior tissue penetration of variable region (VNARs), was considered to have the high antigen binding activity and stability. This type of antibody has a simple structure that can be prokaryoticaly expressed, which makes it easily to produce new antiangiogenic target drugs. Specific anti-IgNAR rabbit multiple antibodies have been used to assess the level of VNARs in sharks and have shown a significant enrichment of IgNAR after triple immunization. An anti-VEGFR2 phage library was used for the targeted VNARs screening, and five candidate VNARs sequences were subsequently obtained by phage screening, followed by combined screening with the transcriptome library, and analysis of conserved regions along with 3D modelling matched the VNAR profile. ELISA and cell-based assays showed that two of the VNARs, VNAR-A6 and VNAR-E3, had a superior antigen affinity and anti-angiogenic activity thereby being able to inhibit human Umbilical Vein Endothelial Cells proliferation and migration. The anti-VEGFR2 VNARs derived from the immunized Chiloscyllium plagiosum and screened by phage library, which provide the new research ideas and specific approaches for the development of new drugs. The anti-VEGFR2 VNARs are capable for blocking the VEGF-VEGFR pathway, which of these may contribute to expanding the use of anti-angiogenic drugs.

Associations of prenatal exposure to PM2.5 and its components with offsprings' neurodevelopmental and behavioral problems: A prospective cohort study from China.

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14-1.18 per µg/m3 in the first trimester; 1.15, 1.12-1.17 in the second trimester; 1.06, 1.04-1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Enhancing Emission and Stability in Na-Doped Cs3Cu2I5 Nanocrystals.

Lead-free Cs3Cu2I5 metal halides have garnered significant attention recently due to their non-toxic properties and deep-blue emission. However, their relatively low photoluminescence quantum efficiency and poor stability have limited their applications. In this work, sodium iodide (NaI) is used to facilitate the synthesis of Cs3Cu2I5 nanocrystals (NCs), demonstrating improved photoluminescence intensity, photoluminescence quantum yield, and stability. Systematic optoelectronic characterizations confirm that Na+ is successfully incorporated into the Cs3Cu2I5 lattice without altering its crystal structure. The improved Photoluminescence Quantum Yield (PLQY) and stability are attributed to the strengthened chemical bonding, which effectively suppresses vacancy defects in the lattice. Additionally, light-emitting diodes (LEDs) based on 10% NaI-doped Cs3Cu2I5 NCs were assembled, emitting vibrant blue light with a maximum radiant intensity of 82 lux and Commission Internationale de l'Eclairage (CIE) chromaticity coordinates of (0.15, 0.1). This work opens new possibilities for commercial lighting display applications.

Cross-Phenotype GWAS Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

Objective: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype GWAS meta-analysis. Methods: We performed cross-phenotype GWAS meta-analysis and colocalization analysis for SSc and PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. Results: We detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 non-HLA loci that reached genome-wide significance (p < 5 × 10-8). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. Conclusion: Our study supports a strong shared genetic susceptibility between SSc and PBC. Through cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Bionic nanopore recognition receptors for single-molecule enantioselectivity studies of chiral drugs.

BACKGROUND: Enantiodiscrimination of chiral drugs is critical for understanding physiological phenomena and ensuring medical safety. Although enantiomers of these drugs share identical physicochemical properties, they exhibit significant differences in pharmacodynamic, pharmacokinetic, and toxicological properties due to the differences in their three-dimensional shapes. Therefore, the development of effective methods for chiral recognition is of great significance and has been a hot topic in chemo/biological studies. RESULTS: In this study, we designed a recognition receptor comprising a α-hemolysin (α-HL) nanopore and sulfobutyl ether-ß-cyclodextrin (SBEßCD) for identifying the enantiomers of the antidepressant duloxetine at the single-molecule level. Chiral molecules were discriminated based on the different current blockages within the recognition receptor. The results indicated a strong interaction between R-duloxetine and the recognition receptor. By combining the experimental data and molecular docking results, we explored the recognition mechanism of the designed nanopore recognition receptor for chiral drug molecules. It was found that hydrophobic and electrostatic interactions play key roles in chiral recognition. Additionally, by comparing the binding kinetics of enantiomers to cyclodextrins in confined nanospace and bulk solution, we found that enantiomeric identification was better facilitated in the confined nanospace. Finally, the enantiomeric excess (ee) of the enantiomeric duloxetine mixture was measured using this recognized receptor. SIGNIFICANCE: This strategy has the advantages of low cost, high sensitivity, and no need for additional derivative modifications, providing a new perspective on the development of chiral recognition sensors with excellent enantioselectivity in drug design, pharmaceuticals, and biological applications.

Nanopore-Based Single-Molecule Investigation of Cation Effect on the i-Motif Structure.

The i-motif, a secondary structure of a four-helix formed by cytosine-rich DNA (i-DNA) through C-C+ base pairing, is prevalent in human telomeres and promoters. This structure creates steric hindrance, thereby inhibiting both gene expression and protein coding. The conformation of i-DNA is intricately linked to the intracellular ionic environment. Hence, investigating its conformation under various ion conditions holds significant importance. In this study, we explored the impact of cations on the i-motif structure at the single-molecule level using the α-hemolysin (α-HL) nanochannel. Our findings reveal that the ability of i-DNA to fold into the i-motif structure follows the order Cs+ > Na+ > K+ > Li+ for monovalent cations. Furthermore, we observed the interconversion of single-stranded DNA (ss-DNA) and the i-motif structure at high and low concentrations of Mg2+ and Ba2+ electrolyte solutions. This study not only has the potential to extend the application of i-motif-based sensors in complex solution environments but also provides a new idea for the detection of metal ions.

Evaluation of pathological response to neoadjuvant chemotherapy in locally advanced cervical cancer.

Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

αPD-1 immunotherapy promotes IL-17A production and promotes the formation of acute radiation-induced lung injury.

BACKGROUND: Radiotherapy (RT) is essential in the treatment of thoracic neoplasms. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have significantly improved the clinical management of non-small cell lung carcinoma (NSCLC). OBJECTIVE: This study aimed to investigate the impact of combining anti-PD-1 (αPD-1) immunotherapy with radiotherapy on lung injury. Additionally, it investigates the role and mechanism of interleukin (IL)-17A, a pro-inflammatory cytokine involved in immune regulation, in lung injury arising from this combination treatment. METHODS: Experiments were conducted using a PD-1 deficient mouse model to simulate acute radiation-induced lung injury. Inbred female BALB/c wild-type (WT) mice and PD-1-/- mice were divided into six groups: WT group, PD-1-/- group, WT_LIR + IgG group, PD-1-/-_LIR + IgG group, WT_LIR + αIL-17A group, and PD-1-/-_LIR + αIL-17A group. The mice were subjected to 8 Gy × 3 irradiation in both lungs. Various methods including histological scoring, immunofluorescence, qPCR, and flow cytometry were employed to analyze the role of IL-17A in lung injury and the effect of PD-1 gene deletion on the severity of radiation-induced lung injury. RESULTS: The PD-1-/-_LIR mice exhibited evident radiation-induced lung injury after receiving 8 Gy × 3 doses in both lungs. The expression level of IL-17A peaked at 2 weeks. Lung injury-related factors IFN-γ, TNF-α, IL-6, and RORγt in the PD-1-/-_LIR groups increased 2 weeks after irradiation. The CD4+ and CD8+ T cells in lung tissue of the PD-1-/-_LIR mice significantly increased. Post αIL-17A administration, the incidence of alveolitis in the treatment group decreased, the expression levels of lung injury-related factors IFN-γ, TNF-α, IL-6, RORγt, TGF-ß1, and IL-17A decreased, and the CD4+ and CD8+ T cells in lung tissue significantly declined. Throughout the observation period, the survival rate of the mice in the treatment group was significantly higher than that of the isotype control group (60% vs 0%, P = 0.011). CONCLUSION: Combining αPD-1 immunotherapy with radiotherapy in mice can induce radiation-induced lung injury, with IL-17A playing a critical role in this process. αIL-17A administration significantly mitigated radiation-induced lung injury caused by the combination of αPD-1 immunotherapy and radiotherapy, improving mouse survival. This finding offers a promising treatment target for lung injury resulting from the combination of αPD-1 immunotherapy and radiotherapy.

Prognostic value of cranial ultrasound findings in infants aged <90 days with bacterial meningitis: a single-centre retrospective cohort study.

BACKGROUND: Bacterial meningitis (BM) poses a serious threat to infant health. We assessed cranial ultrasound (CUS) changes in infants with BM as possible predictors of the neurological sequelae of BM. METHODS: We retrospectively assigned 132 infants diagnosed with BM from 2007 to 2021. Neuroimaging characteristics and cerebral blood flow (CBF) profiles identified using CUS were analysed and compared between the groups during the acute and postacute phases of BM. RESULTS: Overall, 102 infants with CUS and outcome data were recruited. 37/102 (36.3%) infants with neurological developmental impairments comprised the group with sequelae. Abnormal CUS findings increased the risk of sequelae during the postacute phase compared with the acute phase of BM. Prolonged white matter hyperechogenicity was an independent risk factor for sequelae. The CBF profiles of the group with sequelae showed that anterior cerebral artery resistance and pulsatility indices decreased during the acute phase, whereas the mean flow velocity of the middle cerebral artery significantly increased during the postacute phase. Changes in the CBF profiles did not significantly differ in the group without sequelae. CONCLUSIONS: Serial CUS can facilitate the prognostic assessment of infants aged <90 days with BM. Prolonged white matter hyperechogenicity, brain volume loss and cerebral perfusion disorders contribute to the risk of sequelae.