Effects of acetylated polysaccharide on the prebiotic properties of grape seed proanthocyanidins - Based on in vitro fermentation with Artemisia sphaerocephala Krasch glucomannan.

This study evaluated the impact of Artemisia sphaerocephala Krasch glucomannan with different degrees of acetyl group substitution (DS) on the prebiotic properties of grape seed proanthocyanidins (GSP). UV spectra, CIELab, and dynamic light scattering analyses indicated DS-influenced variable interactions between GSP and glucomannan. In vitro fermentation demonstrated that glucomannan enhanced the solubility of some phenolic compounds, and decreased the pH value of fermentation liquids. The production of acetate acid and total short chain fatty acids in the GSP fermentation liquid increased with the degree of DS of glucomannan. Notably, acetylated glucomannan exerted dramatic effects on GSP-induced gut microbiota modulation. The relative abundances of Bacteroides ovatus and Bacteroides decreased as DS increased. Meanwhile, Bacteroides acidifaciens and Akkermansia muciniphila have a positive correlation, even though the GSP-promoted enrichment of A. muciniphila was inhibited by the added glucomannan. Moreover, glucomannan enhanced the metabolism of nucleotides, secondary bile acid, and glycan inhibited by GSP. These findings suggest that acetylated glucomannan affect the prebiotic properties of GSP with its DS serving as a key factor.

Different Degeneration Patterns of Paraspinal Muscles Between Double-Level and Single-Level Lumbar Spondylolisthesis: An Magnetic Resonance Imaging Analysis of 140 Patients.

OBJECTIVE: To evaluate the degeneration patterns of paraspinal muscles in double-level degenerative lumbar spondylolisthesis (dl-DLS) versus single-level degenerative lumbar spondylolisthesis (sl-DLS). METHODS: A total of 67 dl-DLS and 73 sl-DLS patients were included. Multifidus (MF), erector spinae (ES), and psoas major (PM)'s fatty infiltration (FI) and relative cross-sectional area (rCSA) were measured. Sagittal parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) were also assessed. Comparisons and correlation analysis were performed between the 2 groups. RESULTS: MF atrophy is worse in dl-DLS patients from L3-4 to L5-S1, with higher FI from L1-2 to L5-S1 compared to sl-DLS patients. ES atrophy and FI are more pronounced in dl-DLS patients from L1-2 to L5-S1. PM atrophy is more significant in dl-DLS patients at L2-3 to L5-S1, with heavier FI from L1-2 to L3-4, though no difference in FI from L4-5 to L5-S1. The rCSA and FI of MF and ES show significant differences between adjacent segments in both groups, except for MF rCSA between L3-4 and L4-5 in dl-DLS. In dl-DLS, PM rCSA negatively correlates with PT from L4-5 to L2-3, while FI of MF and ES in L5-S1 positively correlates with LL. In sl-DLS, PM FI in L4-5 and L5-S1 negatively correlates with LL. CONCLUSION: Degeneration of MF, ES, and PM is more severe in dl-DLS patients, particularly at the spondylolisthesis level. Severe paraspinal muscle degeneration can lead to spinal force imbalance and progression from sl-DLS to dl-DLS. The degradation of PM and ES correlates negatively with PT and SVA, indicating a link to pelvic decompensation and SVA abnormalities, potentially causing disproportionate degenerative changes in dl-DLS patients.

Application value of individualized tube voltage, contrast injection, and adaptive statistical iterative reconstruction V algorithm based on body mass index in renal computed tomography angiography for radiation and iodinated contrast dose reduction.

OBJECTIVES: To explore the application value of body mass index (BMI)-based kilovoltage peak (kVp) selection and contrast injection protocol combined with different adaptive statistical iterative reconstruction V (ASIR-V) strengths in renal computed tomography angiography (CTA) in reducing radiation and contrast medium (CM) doses. METHODS: One-hundred renal CTA patients were prospectively enrolled and were divided into individualized kVp group (group A, n = 50) and conventional 100 kVp group (group B, n = 50), both with automatic tube current modulation and CM of Iohexol at 350 mgI/mL concentration. Group A: 70 kVp, noise index (NI) of 18 and CM dose rate of 17 mgI/kg/s for 10 s for BMI <25 kg/m2 patients; 80 kVp, NI = 17, and CM dose rate of 19 mgI/kg/s for 10 s for 25 kg/m2≤BMI≤30 kg/m2 patients. Group B: 100 kVp, 50 mL of CM at the flow rate of 4.5 mL/s. The objective image quality, effective radiation dose, CM dose, injection rate, and image quality were compared between the 2 groups. RESULTS: There was no significant difference in patient characteristics between the 2 groups (P > .05). Compared to group B, group A significantly reduced effective radiation dose by 28.4%, CM dose by 27.2%, and injection rate by 22.7% (all P < .001). The 2 groups had similar SD values in erector spine (P > .05). Group A had significantly higher CT values, SNR, and CNR values of the renal arteries than group B (all P < .001). The 2 radiologists had excellent agreement (Kappa value > 0.8) in the subjective scores of renal CTA images and showed no statistically significant difference between the 2 groups (4.57 ± 0.42 vs 4.41 ± 0.49) (P > .05). CONCLUSIONS: BMI-based scan and reconstruction protocol in renal CTA significantly reduces radiation and contrast doses while maintaining diagnostic image quality. ADVANCES IN KNOWLEDGE: (i) BMI-based individualized tube voltage selection and contrast injection protocol in renal CTA reduces both radiation and contrast doses over conventional protocol. (ii) The combination of lower kVp and higher weight ASIR-V maybe used to improve image quality in terms of contrast enhancement and image noise under lower radiation and contrast dose conditions. (iii) Renal CTA of normal size (BMI ≤ 30 kg/m2) patients acquired at low radiation dosage and low iodine contrast dose through the combination of low tube voltage and ASIR-V algorithm achieves excellent diagnostic image quality with a good inter-rater agreement.

Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation.

BACKGROUND: In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown. METHODS: A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis. RESULTS: L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1st vs.2nd vs.3rd generations, ORR: 15.8% vs.56.5% vs.46.7%, P=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, P=0.002). This finding consistently held for patients without CNS metastases (1st vs.2nd vs.3rd generations, median PFS:6.0 vs.18.2 vs.14.1 months, P=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1st/2nd-generation vs.3rd-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, P=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI. CONCLUSIONS: The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.

Perspective in the Mechanisms for Repairing Sperm DNA Damage.

DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.

Label-Free Raman Spectroscopy for Assessing Purity and Maturation of hiPSC-Derived Cardiac Tissue.

I. BACKGROUND: Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) have been utilized in drug toxicity evaluation, drug discovery, and treating heart failure patients, showing substantial effects. Ensuring the quality, purity, and maturation of hiPSC-CMs during large-scale production is crucial. There is a growing demand for a novel method to characterize cell molecular profiles without labels and without causing damage. II. METHODS: In this study, we employed label-free Raman microscopy to evaluate hiPSC-derived CMs. The study involved the characterization of cell molecular profiles without labels and without causing damage. The correlation between Raman spectroscopy of specific components, such as cytochrome c and myoglobin, and CM purity and maturation following hiPSC differentiation was investigated. Additionally, the validation of this correlation was performed by assessing mixtures of commercially available CMs (iCell cardiomyocytes2) and fibroblasts at various ratios as well as hiPSC-derived CMs with different efficiencies. Furthermore, CMs were matured using rapid pacing of traveling waves, and the Raman profiles of matured CMs were compared to those of immature ones. III. RESULTS: Raman spectroscopy indicated that the cytochrome c and myoglobin showed correlation with the purity and maturation of CMs following differentiation of hiPSCs. This correlation was validated through experiments involving different CM-fibroblast mixtures and hiPSC-derived CMs with varying efficiencies. Moreover, matured CMs exhibited markedly different Raman profiles compared to immature ones, indicating the potential of Raman imaging as a tool for assessing CM maturation. IV. CONCLUSIONS: We discovered that Raman spectroscopy of certain components, such as cytochrome c and myoglobin, correlates with the CM purity and maturation following hiPSC differentiation. The findings of this study highlight the potential of label-free Raman microscopy as a nondestructive, high-content, and time-efficient method for quality control of hiPSC-derived CMs. This approach could significantly contribute to ensuring the quality and maturity of hiPSC-CMs for various applications in drug discovery and regenerative medicine.

Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma.

PURPOSE: To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients. METHODS: 357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test. RESULTS: The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001). CONCLUSION: The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.

Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis.

Spermatogonial stem cells (SSCs) play a crucial role in the male reproductive system, responsible for maintaining continuous spermatogenesis. The microenvironment or niche of SSCs is a key factor in regulating their self-renewal, differentiation and spermatogenesis. This microenvironment consists of multiple cell types, extracellular matrix, growth factors, hormones and other molecular signals that interact to form a complex regulatory network. This review aims to provide an overview of the main components of the SSCs microenvironment, explore how they regulate the fate decisions of SSCs, and discuss the potential impact of microenvironmental abnormalities on male reproductive health.

Pan-cancer exploration of PNO1: A prospective prognostic biomarker with ties to immune infiltration.

The partner of NOB1 homolog (PNO1) is an RNA-binding protein that participates in ribosome biogenesis and protein modification. The functions of this molecule are largely unknown in cancers, particularly breast cancer. We employed bioinformatics methods to probe the putative oncogenic functions of PNO1 based on expression profiles and clinical data from the cancer genome atlas (TCGA), genotype-tissue expression project (GTEx), human protein atlas (HPA), cancer cell line encyclopedia (CCLE), UALCAN, drug sensitivity in cancer (GDSC) and UCSC XENA databases. Our analyses revealed that PNO1 was overexpressed in 31 malignancies, which excluded kidney chromophobe (KICH) and acute myeloid leukemia (LAML). Prognostic assessments have demonstrated that high PNO1 expression was significantly correlated with poor overall and disease-specific survival in various cancers. The promoter methylation level of PNO1 is significantly decreased in breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), prostate adenocarcinoma (PRAD), thyroid carcinoma (THCA) and uterine corpus endometrial carcinoma (UCEC). Furthermore, inhibition of PNO1 decreased the viability, migration and invasion of breast cancer cells, and these results were confirmed by mouse xenograft models of breast cancer. In addition, we discovered that tumor microenvironment (TME), immune infiltration, and chemotherapy sensitivity were influenced by PNO1 expression. Concordantly, our analyses revealed a significant positive correlation between PNO1 and programmed cell death ligand 1 (PD-L1) expression across breast carcinoma samples. In conclusion, these findings indicate that PNO1 could act as a promising prognostic biomarker and adjunct diagnostic indicator, because it affects tumor growth and invasion. Our study offers valuable new perspectives on the oncogenic role of PNO1 in various types of cancers.

Safety and efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis.

Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR. Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis. Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups. Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909.

An ultrasensitive electrochemical biosensor with dual-amplification mode and enzyme-deposited silver for detection of miR-205-5p.

An electrochemical biosensor based on dual-amplified nucleic acid mode and biocatalytic silver deposition was constructed using catalytic hairpin assembly-hybrid chain reaction (CHA-HCR). The electrochemical detection of silver on the electrode by linear sweep voltammetry (LSV) can be utilized to quantitatively measure miR-205-5p since the amount of silver deposited on the electrode is proportional to the target nucleic acid. The current response values exhibit strong linearity with the logarithm of miR-205-5p concentrations ranging from 0.1 pM to 10 µM, and the detection limit is 28 fM. A consistent trend was found in the results of the qRT-PCR and electrochemical biosensor techniques, which were employed to determine the total RNA recovered from cells, respectively. Moreover, the constructed sensor was used to assess miR-205-5p on various cell counts, and the outcomes demonstrated the excellent analytical efficiency of the proposed strategy. The recoveries ranged from 97.85% to 115.3% with RSDs of 2.251% to 4.869% in human serum samples. Our electrochemical biosensor for miR-205-5p detection exhibits good specificity, high sensitivity, repeatability, and stability. It is a potentially useful sensing platform for tumor diagnosis and tumor type identification in clinical settings.

Effectiveness of COVID-19 Vaccination against Severe Symptoms and Death Among Geriatric Inpatients: A Retrospective Cohort Study in Macao.

Monitoring the effectiveness of COVID-19 vaccination is critical for understanding if the vaccinated population, especially the elderly, is adequately protected from the emergence of new SARS-CoV-2 variants. This study aimed to investigate the effects of COVID-19 vaccination on the severity of symptoms and mortality in hospitalized geriatric patients during the Omicron BF.7 surge in Macao. Data from electronic health records and vaccination registry of inpatients aged 60 years or above admitted to Kiang Wu Hospital from 12 December 2022 to 12 March 2023 were retrospectively analyzed. The study involved 848 people, including 426 vaccinated and 422 unvaccinated individuals. The mean CXR scores (8.95 ± 9.49 vs. 11.41 ± 10.81, p < 0.001) and the mean MEWS scores (0.96 ± 2.01 vs. 1.49 ± 2.45, p < 0.001) were lower in the vaccinated group. By comparing the dose counts, no significant difference was seen in the odds of death. Based on the time of the last vaccination, 128 people were categorized as complete and 298 as incomplete vaccination. The complete vaccination group showed a 54% (95% CI 0.23-0.91) reduction in mortality risk (p = 0.026). The study findings not only reconfirm the effectiveness of COVID-19 vaccination but, more importantly, highlight the importance of vaccination timing to maximize vaccines' protective effect.

How digital transformation enhances corporate innovation performance: The mediating roles of big data capabilities and organizational agility.

Digital transformation has emerged as a key driver of high-quality enterprise development and an essential tool in forging an innovation-driven paradigm.Existing studies fail to delve into the specific mechanisms of their impact on firms' innovation performance, and views on their impact are divergent. Some studies suggest that digital transformation can enhance innovation performance, while others point out that it may have negative impacts, and cannot clearly answer how big data capabilities and organisational agility play a role in the digital transformation process. Therefore, based on dynamic capability theory and systems engineering theory, this study adopts the logical framework of "strategy-behaviour-performance" to systematically explore the process of digital transformation that enhances firms' innovation performance through the enhancement of big data capability and organisational agility. By empirically analysing the survey data of 476 manufacturing enterprises in China, the study reveals the chain-mediated effects of big data capability and organisational agility, and confirms the key roles of both in the transformation process. The findings suggest that digital transformation significantly improves firms' innovation performance, and that the dual mediating effects of big data capability and organisational agility are important links in its influencing mechanism. These findings not only provide empirical support for the theoretical model of digital transformation, but also provide practical guidance for enterprises to formulate strategies and optimise resource allocation in the digital era. We suggest that enterprises should strengthen the cultivation of big data capabilities and organisational agility while promoting digital transformation to better adapt to and lead market changes.

Selenite improves growth by modulating phytohormone pathways and reprogramming primary and secondary metabolism in tomato plants.

Selenium (Se) is an essential micronutrient in organisms that has a significant impact on physiological activity and gene expression in plants, thereby affecting growth and development. Humans and animals acquire Se from plants. Tomato (Solanum lycopersicum L.) is an important vegetable crop worldwide. Improving the Se nutrient level not only is beneficial for growth, development and stress resistance in tomato plants but also contributes to improving human health. However, the molecular basis of Se-mediated tomato plant growth has not been fully elucidated. In this study, using physiological and transcriptomic analyses, we investigated the effects of a low dosage of selenite [Se(Ⅳ)] on tomato seedling growth. Se(IV) enhanced the photosynthetic efficiency and increased the accumulation of soluble sugars, dry matter and organic matter, thereby promoting tomato plant growth. Transcriptome analysis revealed that Se(IV) reprogrammed primary and secondary metabolic pathways, thus modulating plant growth. Se(IV) also increased the concentrations of auxin, jasmonic acid and salicylic acid in leaves and the concentration of cytokinin in roots, thus altering phytohormone signaling pathways and affecting plant growth and stress resistance in tomato plants. Furthermore, exogenous Se(IV) alters the expression of genes involved in flavonoid biosynthesis, thereby modulating plant growth and development in tomato plants. Taken together, these findings provide important insights into the regulatory mechanisms of low-dose Se(IV) on tomato growth and contribute to the breeding of Se-accumulating tomato cultivars.

A Retrospective Cohort Study on Treponema pallidum Infection: Clinical Trends and Treatment Outcomes for Congenital Syphilis in Guangxi, China (2013-2023).

Background: Syphilis, a prevalent sexually transmitted infection, poses severe risks, especially during pregnancy. This study aimed to elucidate the trends and impacts of syphilis in Guangxi, China, focusing on prevalence, clinical manifestations, and treatment outcomes in pregnant women and newborns. The objectives included understanding the demographic characteristics of affected pregnant women, analysing the clinical manifestations in newborns, and assessing the effectiveness of the treatment protocol. Methods: Conducted in adherence to ethical guidelines, a retrospective cohort study from January 2013 to December 2023 included 54,048 pregnant women tested for T. pallidum. Diagnosis involved a comprehensive approach, utilizing tests like the Toluidine Red Unheated Serum Test (TRUST) and the Treponema pallidum Particle Agglutination (TPPA) assay. Infant diagnosis and clinical manifestations were evaluated through a decade-long follow-up. Treatment protocols, including Benzathine penicillin, were implemented. Statistical analyses were conducted using SAS version 9.4. Results: Among 54,048 pregnant women, 0.10% were syphilis positive, correlating with a rise in hospitalizations. Newborns exhibited varied clinical manifestations, with neonatal pneumonia and jaundice being prevalent. The treatment protocol, especially with Benzathine penicillin, achieved a remarkable 100% cure success rate. The study noted a significant reduction in mother-to-child transmission. Syphilis in mothers and babies was diagnosed at different clinical stages, including primary, secondary, latent, and tertiary. Conclusion: This study underscores the escalating impact of syphilis on pregnant women and newborns in Guangxi, China. The findings highlight the necessity for robust preventive measures, early diagnosis, and effective treatment strategies. The observed 100% cure success rate with Benzathine penicillin emphasizes the importance of strict treatment protocols in mitigating the adverse effects of congenital syphilis and reducing its transmission.

Physiological and molecular responses of strawberry plants to Cd stress.

Cadmium (Cd), a toxic metal element, can be absorbed by plants via divalent metal ion transporters, thereby retarding plant growth and posing a threat to human health. Strawberries are popular and economically valuable berry species that are sensitive to soil pollutants, especially Cd. However, the mechanisms underlying Cd stress responses in strawberry plants remain largely unclear. Here, we investigated the physiological and molecular basis of Cd stress responses in strawberry plants using the diploid strawberry 'Yellow Wonder' as a material. The results indicated that Cd stress induced oxidative damage, repressed photosynthetic efficiency, and interfered with the accumulation and redistribution of trace elements. Furthermore, Cd stress reduced the concentrations of indoleacetic acid, trans-zeatin riboside and gibberellic acid while increasing the concentration of abscisic acid, thus altering the phytohormone signaling pathway in strawberry plants. Cd stress also inhibited the expression of genes involved in nitrogen uptake and assimilation while promoting the energy supply for plant survival under Cd toxicity. Moreover, the flavonoid biosynthesis pathway was induced, and the anthocyanin concentration increased, thereby improving the free radical scavenging capacity of strawberry plants under Cd toxicity. Additionally, we identified several transcription factors and functional genes as hub genes based on a weighted gene coexpression network analysis. These results collectively provide a theoretical foundation for strawberry breeding and ensuring agriculture and food safety.

Sulfoxide-containing polymers conjugated prodrug micelles with enhanced anticancer activity and reduced intestinal toxicity.

Poly(ethylene glycol) (PEG) is widely utilized as a hydrophilic coating to extend the circulation time and improve the tumor accumulation of polymeric micelles. Nonetheless, PEGylated micelles often activate complement proteins, leading to accelerated blood clearance and negatively impacting drug efficacy and safety. Here, we have crafted amphiphilic block copolymers that merge hydrophilic sulfoxide-containing polymers (psulfoxides) with the hydrophobic drug 7-ethyl-10-hydroxylcamptothecin (SN38) into drug-conjugate micelles. Our findings show that the specific variant, PMSEA-PSN38 micelles, remarkably reduce protein fouling, prolong blood circulation, and improve intratumoral accumulation, culminating in significantly increased anti-cancer efficacy compared with PEG-PSN38 counterpart. Additionally, PMSEA-PSN38 micelles effectively inhibit complement activation, mitigate leukocyte uptake, and attenuate hyperactivation of inflammatory cells, diminishing their ability to stimulate tumor metastasis and cause inflammation. As a result, PMSEA-PSN38 micelles show exceptional promise in the realm of anti-metastasis and significantly abate SN38-induced intestinal toxicity. This study underscores the promising role of psulfoxides as viable PEG substitutes in the design of polymeric micelles for efficacious anti-cancer drug delivery.

Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 µm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

Physiological and molecular bases of the nickel toxicity responses in tomato.

Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.