Association of Perioperative Skeletal Muscle Index Change With Outcome in Colorectal Cancer Patients.

BACKGROUND: The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients. METHODS: This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: highpre-highpost, highpre-lowpost, lowpre-highpost and lowpre-lowpost. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models. RESULTS: A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with highpre-highpost, those with highpre-lowpost (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with lowpre-lowpost were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with lowpre-highpost had similar risk of RFS compared to those with highpre-highpost at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05). CONCLUSIONS: Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.

The impact of standardized robotics course training during colorectal surgery fellowship on post-training practice: a survey of graduates.

The Association of Program Directors for Colon and Rectal Surgery (APDCRS) has sponsored a standardized robotics course for colorectal and minimally invasive surgery fellows since 2011. The study objective was to assess the impact of the APDCRS-sponsored course on surgical approaches adopted by young colorectal surgeons before, during, and after fellowship. An internet-based survey was administered to 2014-2022 ACGME-accredited colorectal surgery program graduates. Study variables were summarized using frequencies and proportions. Survey response rate was 43.2%. Laparoscopic and robotic volumes were consistently higher than open and hand-assist laparoscopic volumes over the study period. About 70.0% of fellows performed ≥ 20 laparoscopic cases before 2017, and over 80% had experience with ≥ 20 laparoscopic cases during/after 2017. An increasing trend of performing ≥ 20 robotic colorectal cases during fellowship was observed (before 2017: 75.0%, 2018-2019: 76.9%, and 2021-2022: 84.8%). Multivariate logistic regression analysis showed that higher robotic volume (≥ 25 colorectal cases) during general surgery residency increased odds of performing ≥ 50 robotic cases during fellowship (OR: 4.38, 95% CI 0.88, 26.1). Higher robotic volumes during fellowship correlated with higher robotic volumes in the first year of post-fellowship practice. 88.6% of respondents agree (21.0%) or strongly agree (67.6%) that the APDCRS robotics training course met expectations, and 83.8% agree or strongly agree that the course prepared them for post-graduate robotics practice. The APDCRS-sponsored robotics training course met expectations and prepared colorectal surgery fellows for adopting the robotic approach after graduation, with the majority of respondents reporting that they utilize robotics in their post-graduation colorectal practice.

IL-27 attenuated macrophage injury and inflammation induced by Mycobacterium tuberculosis by activating autophagy.

Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1ß, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB.

Tanshinone T1/T2A facilitate let-7 to suppress non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Tanshinones are a group of compounds in Salvia miltiorrhiza. Although the effects of tanshinone Ⅰ (T1) and tanshinone ⅡA (T2A) are widely concerned, the mechanism of T1 and T2A in lung cancer is rarely studied. EXPERIMENTAL PROCEDURE: Xenograft tumor growth was performed to detect the role of T1/T2A in vivo. Next-generation sequencing of miRNA expression profiles in T1/T2A-treated A549 cells showed that T1/T2A upregulated the expression of the let-7 family. Then, let-7a-5p and its downstream target gene BORA were identified as the research objects in this paper. Mechanistically, we examined the interplay between miR-let-7 and BORA through the dual-luciferase reporter assay. Finally, the potential regulatory role of T1/T2A on Lin28B or MYC was explored. RESULTS: This study found that the let-7 family was significantly up-regulated via "Next-generation" sequencing (NGS) in the T1/T2A-treated A549 cell line, while BORA was downregulated. BORA was confirmed as a direct target of let-7. LncRNA MYCLo-5 was up-regulated after treatment with tanshinones. Knockdown of MYCLo-5 promoted the cell cycle and proliferation of non-small cell lung cancer (NSCLC). CONCLUSIONS: This study explored the effect of tanshinone T1 and T2A on NSCLC in vitro and in vivo, revealing the T1/T2A- let-7/ BORA /MYCLo-5 regulatory pathway, which provided new ideas for lung cancer treatment.

An Antisense Long Non-Coding RNA, LncRsn, Is Involved in Sexual Reproduction and Full Virulence in Fusarium graminearum.

Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a devastating crop disease that leads to significant declines in wheat yield and quality worldwide. Long non-coding RNAs (lncRNAs) are found to play significant functions in various biological processes, but their regulatory functions in the sexual reproduction and pathogenicity of F. graminearum have not been studied extensively. This study identified an antisense lncRNA, named lncRsn, located in the transcription initiation site region between the 5'-flanking gene FgSna and the 3'-flanking gene FgPta. A deletion mutant of lncRsn (ΔlncRsn) was constructed through homologous recombination. ΔlncRsn exhibited huge reductions in pathogen and sexual reproduction. Additionally, the deletion of lncRsn disrupted the biosynthesis of deoxynivalenol (DON) and impaired the formation of infection structures. RT-qPCR analysis reveals that lncRsn may negatively regulate the transcription of the target gene FgSna. This study found that lncRsn plays an important role in sexual and asexual reproduction, pathogenicity, virulence, osmotic stress, and cell wall integrity (CWI) in F. graminearum. Further characterization of pathogenesis-related genes and the reaction between lncRsn and protein-coding genes will aid in developing novel approaches for controlling F. graminearum diseases.

Osthole attenuates asthma-induced airway epithelial cell apoptosis and inflammation by suppressing TSLP/NF-κB-mediated inhibition of Th2 differentiation.

OBJECTIVE: The aim of this study was to investigate the influence of osthole (OS) on asthma-induced airway epithelial cell apoptosis and inflammation by restraining Th2 differentiation through suppressing TSLP/NF-κB. METHODS: An asthma mouse model and an inflammation cell model were constructed with ovalbumin (OVA) and lipopolysaccharide (LPS), respectively. CD4 + T cells were treated with IL-4 to induce Th2 differentiation. Model mice were treated with OS (15,40 mg/kg) for 7 days, and 10 µg/mL OS was added to cell treatment groups. The levels of relevant indices were detected by RT‒qPCR, HE and Masson staining, Western blotting, ELISA and flow cytometry. RESULTS: In a mouse asthma model, TSLP expression was elevated, and the NF-κB pathway was activated. Therefore, OS could restrain the apoptosis and inflammation of airway epithelial cells. Downstream mechanistic studies revealed that OS can suppress Th2 differentiation by restraining the level of TSLP and NF-κB nuclear translocation, thus facilitating the proliferation of airway epithelial cells, restraining their apoptosis and inflammation, and alleviating airway inflammation in asthmatic mice. CONCLUSION: OS can inhibit Th2 differentiation by inhibiting the TSLP and NF-κB pathways, which can reduce the apoptosis and inflammation of airway epithelial cells caused by asthma.

Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF.

BACKGROUND: Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection (STI) that can result in pelvic inflammatory disease, ectopic pregnancy and infertility in women. Currently, there is no prophylactic vaccine. METHODS: This study examined T cell immunity in a cohort of women recently infected with CT. Participants were screened against peptides spanning 33 of 894 possible CT proteins, either ex vivo or using short-term cell lines (STCL). CT-specific T cells were characterized by IFN-γ ELISpot and flow cytometry. RESULTS: Ex vivo CT-specific T cells were rarely detected; however, following in vitro expanded CT-specific T cells were detected by IFN-γ ELISpot in 90% (27/30) of participants. Notably, over 50% of participants had T cell responses targeting chlamydial protease-like activity factor (CPAF). T cell epitopes were dispersed across the CPAF protein. Flow cytometry analysis of STCL found CT-specific cells, were mainly CD4+, produced IFN-γ and TNF-α and were sustained over 12 months. Ex vivo analysis suggested CT-specific T cells mostly exhibited a central memory phenotype. CONCLUSION: Our results indicate that CT infection elicits low-frequency, persistent CD4 T cell responses in most women and that the secreted protein, CPAF, is an immunoprevalent CT antigen. Altogether, these data support development and testing of CT vaccines that enhance CD4 T cells against CPAF.

Neurophysiological markers of disease severity and cognitive dysfunction in major depressive disorder: A TMS-EEG study.

Background: Transcranial magnetic stimulation-electroencephalography (TMS-EEG) is a powerful technique to study the neuropathology and biomarkers of major depressive disorder (MDD). This study investigated cortical activity and its relationship with clinical symptoms and cognitive dysfunction in MDD patients by indexing TMS-EEG biomarkers in the dorsolateral prefrontal cortex (DLPFC). Methods: 133 patients with MDD and 76 healthy individuals participated in this study. Single-pulse TMS was performed on the left DLPFC to obtain TMS-evoked potential (TEP) indices. TMS-EEG waveforms and components were determined by global mean field amplitude. We used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to measure participants' cognitive function. Results: Patients with MDD had a lower excitatory P180 index compared to healthy controls, and P180 amplitude was negatively correlated with the severity of depressive and anxiety symptoms in patients with MDD. In the MDD group, P30 amplitude was negatively associated with RBANS Visuospatial/ Constructional index and total score. Conclusions: TMS-EEG findings suggest that abnormal cortical excitation and inhibition induced by TMS on the DLPFC are associated with the severity of clinical symptoms and cognitive dysfunction in patients with MDD. P180 and P30 have the potential to serve as neurophysiological biomarkers of clinical symptoms and cognitive dysfunction in MDD patients, respectively.

Genome-wide investigation of the OR gene family in Helicoverpa armigera and functional analysis of OR48 and OR75 in metamorphosis development.

The cotton bollworm, Helicoverpa armigera, is a significant global agricultural pest, particularly detrimental during its larval feeding period. Insects' odorant receptors (ORs) are crucial for their crop-feeding activities, yet a comprehensive analysis of H. armigera ORs has been lacking, and the influence of hormones on ORs remain understudied. Herein, we conducted a genome-wide study and identified 81 ORs, categorized into 15 distinct groups. Analyses of protein motifs and gene structures revealed both conservation within groups and divergence among them. Comparative gene duplication analysis between H. armigera and Bombyx mori highlighted different duplication patterns. We further investigated subcellular localization and protein interactions within the odorant receptor family, providing valuable insights for future functional and interaction studies of ORs. Specifically, we identified that OR48 and OR75 were abundantly expressed during molting/metamorphosis and feeding stages, respectively. We demonstrated that 20E induced the upregulation of OR48 via EcR, while insulin upregulated OR75 expression through InR. Moreover, 20E induced the translocation of OR48 to the cell membrane, mediating its effects. Functional studies involving the knockdown of OR48 and OR75 revealed their roles in metamorphosis development, with OR48 knockdown resulting in delayed pupation and OR75 knockdown leading to premature pupation. OR48 can promote autophagy and apoptosis in fat body, while OR75 can significantly inhibit apoptosis and autophagy. These findings significantly contribute to our understanding of OR function in H. armigera and shed light on potential avenues for pest control strategies.

Oncogenic tRNA-derived fragment tRF-Leu-CAG promotes tumorigenesis of lung cancer via targeting TCEA3 and increasing autophagy.

BACKGROUND: Lung cancer is a prevalent and severe form of malignant tumors worldwide. tRF-Leu-CAG, a recently discovered non-coding single-stranded small RNA derived from transfer RNA, has sparked interest in exploring its biological functions and potential molecular mechanisms in lung cancer. METHODS: The abundance of tRF-Leu-CAG was measured via quantitative real-time polymerase chain reaction (qRT-PCR) in 96 sets of lung cancer tissue samples obtained from clinical patients. Subsequently, both in vivo and in vitro experiments were conducted to validate the biological functions of tRF-Leu-CAG in lung cancer. Furthermore, an exploration of the potential target genes of tRF-Leu-CAG and its association with autophagy and drug resistance in lung cancer was undertaken. RESULTS: Our analysis revealed a significant upregulation of tRF-Leu-CAG in non-small cell lung cancer (NSCLC) tissues. Additionally, we observed that heightened expression of tRF-Leu-CAG significantly augmented the proliferation and migration of NSCLC cells, facilitated cell cycle progression, and suppressed apoptosis. Furthermore, we identified transcription elongation factor A3 (TCEA3) as a direct target gene of tRF-Leu-CAG. TCEA3 inhibited the proliferation and migration of NSCLC, and tRF-Leu-CAG promoted the proliferation and migration of NSCLC by mediating the silencing of TCEA3. Moreover, we demonstrated that the augmentation of paclitaxel resistance by tRF-Leu-CAG was contingent on autophagy. Finally, tRF-Leu-CAG notably accelerated tumor growth and promoted the process of epithelial-mesenchymal transition (EMT) in vivo. CONCLUSIONS: tRF-Leu-CAG promotes NSCLC tumor growth and metastasis by targeting TCEA3 and promotes paclitaxel resistance by enhancing cellular autophagy. These results provide potentially effective targets and therapeutic options for the clinical treatment of NSCLC.

A novel Anaerobic Cathodic Dynamic Membrane Bioreactor (AnCDMBR) for efficient mitigating fouling and recovering bioenergy from municipal wastewater.

Concerns regarding membrane fouling and suboptimal bioenergy recovery have constrained the implementation of anaerobic membrane bioreactor (AnMBR) for treating low-strength municipal wastewater. This study presents a novel anaerobic cathodic dynamic membrane bioreactor (AnCDMBR) designed to address these challenges. A self-formed cathodic dynamic membrane (CDM) on inexpensive carbon cloth was developed to function as both a membrane and biocathode to achieve dual-function effects of mitigating membrane fouling and accelerating organics conversion. Compared with common dynamic membrane (1.52 kPa/d) and commercial membranes (7.52 kPa/d), the developed CDM presented a significantly reduced fouling rate (1.02 kPa/d), exhibiting the potential as a substitute for high-cost conductive membranes. Furthermore, efficient and stable biomethanation occurred in AnCDMBR with a superior methane yield rate of 0.26 L-CH4/g-COD (CH4 content > 95 %), which was 1.42 times higher than the control, linked to the higher activities of microbial metabolism and methanogenic-related key enzymes. Further analysis revealed that electrostimulation-induced niche differentiation of microbiota regulated interspecies interactions between electroactive microorganisms and complex anaerobic digestion microbiomes, facilitating organic matter conversion to methane and leading to superior bioenergy recovery. This study offered a new strategy for effectively mitigating fouling and recovering bioenergy from low-strength wastewater, potentially expanding the application of AnMBRs.

Amide proton transfer-weighted MRI for assessing rectal adenocarcinoma T-staging and perineural invasion: a prospective study.

OBJECTIVE: To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). METHODS: This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. RESULTS: A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. CONCLUSION: Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. CLINICAL RELEVANCE STATEMENT: Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. KEY POINTS: The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.

Phylogenomics and functional analysis of Glycerol-3-Phosphate Acyltransferase (GPAT) Genes: A critical role in lipid biosynthesis.

The tung tree (Vernicia fordii Hemsl.), an economically important woody plant, is widely planted for the production of high-quality tung oil. Glycerol-3-phosphate acyltransferases (GPATs), the rate-limiting enzymes in triacylglycerol synthesis, play an important role in seed oil biosynthesis. In this study, we performed a genome-wide analysis of VfGPATs. A total of 9 VfGPATs were identified from the whole tung genome, and phylogenetic analysis divided the VfGPATs into three major clades: clade II (VfGPAT9), clade III (VfATS1) and clade IV (VfGPAT1 ~ 8). Subcellular localization analysis revealed that five VfGPATs (1, 5, 6, 8, and 9) are localized in the endoplasmic reticulum, and four VfGPATs (3-1, 3-2, 3-3, and ATS1) are localized in the chloroplast. Overexpression of VfGPATs in Arabidopsis thaliana revealed that the oil content in VfGPAT8- and VfGPAT9-transgenic plants were significantly increased by 26.60 and 55.94% compared to the wild-type. Transient expression of VfGPAT8 + VfFADX and VfGPAT9 + VfFADX could promote the synthesis of α-eleostearic acid and enhance the accumulation of lipid droplets in tobacco (Nicotiana benthamiana) leaves. We further tested the enzymatic activities of VfGPAT8 and VfGPAT9 with the yeast double mutant strain ZAFU1. The results showed that VfGPAT8 complemented the phosphatidate biosynthetic defect in the double mutant, while VfGPAT9 could not, suggesting that VfGPAT8 has a high acetyltransferase activity. However, altering serine (S) residue at position 113 of VfGPAT9 to threonine (T) could restore its enzymatic activity. This study provided important insights into the evolutionary history of VfGPATs and will promote the genetic improvement of tung trees and related species.

Genomic characterization of bZIP gene family and patterns of gene regulation on Cercospora beticola Sacc resistance in sugar beet (Beta vulgaris L.).

Sugar beet (Beta vulgaris L.) is one of the most important sugar crops, accounting for nearly 30% of the world's annual sugar production. And it is mainly distributed in the northwestern, northern, and northeastern regions of China. However, Cercospora leaf spot (CLS) is the most serious and destructive foliar disease during the cultivation of sugar beet. In plants, the bZIP gene family is one of important family of transcription factors that regulate many biological processes, including cell and tissue differentiation, pathogen defense, light response, and abiotic stress signaling. Although the bZIP gene family has been mentioned in previous studies as playing a crucial role in plant defense against diseases, there has been no comprehensive study or functional analysis of the bZIP gene family in sugar beet with respect to biotic stresses. In this study, we performed a genome-wide analysis of bZIP family genes (BvbZIPs) in sugar beet to investigate their phylogenetic relationships, gene structure and chromosomal localization. At the same time, we observed the stomatal and cell ultrastructure of sugar beet leaf surface during the period of infestation by Cercospora beticola Sacc (C. beticola). And identified the genes with significant differential expression in the bZIP gene family of sugar beet by qRT-PCR. Finally we determined the concentrations of SA and JA and verified the associated genes by qRT-PCR. The results showed that 48 genes were identified and gene expression analysis indicated that 6 BvbZIPs were significantly differential expressed in C. beticola infection. It is speculated that these BvbZIPs are candidate genes for regulating the response of sugar beet to CLS infection. Meanwhile, the observation stomata of sugar beet leaves infected with C. beticola revealed that there were also differences in the surface stomata of the leaves at different periods of infection. In addition, we further confirmed that the protein encoded by the SA signaling pathway-related gene BVRB_9g222570 in high-resistant varieties was PR1, which is closely related to systemic acquired resistance. One of the protein interaction modes of JA signal transduction pathway is the response of MYC2 transcription factor caused by JAZ protein degradation, and there is a molecular interaction between JA signal transduction pathway and auxin. Despite previous reports on abiotic stresses in sugar beet, this study provides very useful information for further research on the role of the sugar beet bZIP gene family in sugar beet through experiments. The above research findings can promote the development of sugar beet disease resistance breeding.

An advanced 3D DNA nanoplatform for spatiotemporally confined enhanced dual-mode biosensing MicroRNA in cancer cell.

Dual-mode signal output platforms have demonstrated considerable promise due to their improved anti-interference capability and inherent signal self-correction. Nevertheless, traditional discrete-distributed signal probes often encounter significant drawbacks, including limited mass transfer efficiency, diminished signal strength, and instability in intricate biochemical environments. In response to these challenges, a scalable and hyper-compacted 3D DNA nanoplatform resembling "periodic focusing heliostat" has been developed for synergistically enhanced fluorescence (FL) and surface-enhanced Raman spectroscopy (SERS) biosensing of miRNA in cancer cells. Our approach utilized a distinctive assembly strategy integrating gold nanostars (GNS) as fundamental "heliostat units" linked by palindromic DNA sequences to facilitate each other hand-in-hand cascade alignment and condensed into large scale nanostructures. This configuration was further augmented by the incorporation of gold nanoparticles (GNP) via strong Au-S bonds, resulting in a sturdy framework for improved signal transduction. The initiation of this assembly process was mediated by the hybridization of dsDNA to miRNA-21, which served as a primer for polymerization and nicking reactions, thus generating a multifunctional T2 probe. This probe is intricately designed with three distinct parts: a 3'-palindromic end for structural integrity, a central region for capturing SERS-active probes (Cy3-P2), and a 5'-segment for attaching fluorescence reporters. Upon integration T2 into the GNS-based heliostat unit, it promotes palindromic arm-induced aggregation and plasma exciton coupling between plasma nanoparticles and signal transduction tags. This clustered arrangement creates a high-density "hot spot" array that maximizes the local electromagnetic fields necessary for enhanced SERS and FL response. This superstructure supports enhanced aggregation-induced signal amplification for both SERS and FL, offering exceptional sensitivity with LOD as low as 0.0306 pM and 0.409 pM. The efficacy of this method was demonstrated in the evaluation of miRNA-21 in various cancer cell lines.

Hypopituitarism after gamma knife radiosurgery for pituitary adenomas: long-term results from a single-center experience.

OBJECTIVE: The aim of this study was to investigate the incidence and risk factors of new-onset hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenomas in a single center. METHODS: In this retrospective study, 241 pituitary adenoma patients who underwent GKRS from 1993 to 2016 were enrolled. These patients had complete endocrine, imaging, and clinical data before and after GKRS. The median follow-up time was 56.0 (range, 12.7-297.6) months. RESULTS: Fifty patients (20.7%) developed new-onset hypopituitarism after GKRS, including hypogonadism (n = 22), hypothyroidism (n = 29), hypocortisolism (n = 20), and growth hormone deficiency (n = 4). The median time to new-onset hypopituitarism was 44.1 (range, 13.5-141.4) months. The rates of new-onset hypopituitarism were 7%, 16%, 20%, 39%, and 45% at 1, 3, 5, 10, and 15 years, respectively. For those patients treated with a single GKRS, sex (p = 0.012), suprasellar extension (p = 0.048), tumor volume (≥ 5 cm3) (p < 0.001), tumor progression (p = 0.001), pre-existing hypopituitarism (p = 0.011), and previous surgery (p = 0.009) were significantly associated with new-onset hypopituitarism in univariate analysis. In the multivariate analysis, tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism (hazard ratio [HR] = 3.401, 95% confidence interval [CI] = 1.708-6.773, p < 0.001 and HR = 3.594, 95% CI = 1.032-12.516, p = 0.045, respectively). For patients who received 2 or more times GKRS, no risk factors associated with new-onset hypopituitarism were found. CONCLUSION: New-onset hypopituitarism was not uncommon after GKRS for pituitary adenomas. In this study, large tumor volume (≥ 5 cm3) and tumor progression were associated with new-onset hypopituitarism after a single GKRS.

Pharmacokinetic/Pharmacodynamic modelling of Saxagliptin and its active metabolite, 5-hydroxy Saxagliptin in rats with Type 2 Diabetes Mellitus.

BACKGROUND AND PURPOSES: It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect. METHODS: First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX. RESULTS: A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal Emax model and sigmoidal Emax with E0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration (Tmax=0.11 h, t1/2, ka=0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC50, EC50, 5-OH SAX=0.46EC50, SAX(parent), it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature. CONCLUSIONS: The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.

Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice.

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice. MVA.OmcB or MVA.CPAF increased antigen-specific T cells in CM972-immune mice ∼150 and 50-fold, respectively, but failed to improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost immunization of naïve mice elicited a cluster of differentiation (CD) 8-dominant T-cell response dominated by cluster of differentiation (CD)8 T cells that failed to protect. ChAd.CPAF/ChAd.CPAF prime-boost also induced a CD8-dominant response with a marginal reduction in burden. Challenge of ChAd.CPAF-immunized mice genetically deficient in CD4 or CD8 T cells showed that protection was entirely CD4-dependent. CD4-deficient mice had prolonged infection, whereas CD8-deficient mice had higher frequencies of CPAF-specific CD4 T cells, earlier clearance, and reduced burden than wild-type controls. These data reinforce the essential nature of the CD4 T-cell response in protection from chlamydial genital infection in mice and the need for vaccine platforms that drive CD4-dominant responses.

Interaction effect between blood selenium levels and stroke history on all-cause mortality: a retrospective cohort study of NHANES.

Aim: The study aimed to investigate the interaction effect between blood selenium levels and stroke history on all-cause mortality. Methods: In this retrospective cohort study, participant data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. The covariates were screened via the backward selection method in weighted univariate and multivariate Cox regression models. Weighted univariate and multivariate Cox regression models were conducted to investigate the association of blood selenium and stroke history with all-cause mortality. The results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). The synergy index (SI) was used to assess the assistive interaction. The association was further explored in different gender groups. Results: Totally, 8,989 participants were included, of whom 861 (9.57%) died. Participants with blood selenium ≥192.96 ug/L were associated with lower odds of all-cause mortality (HR = 0.70, 95% CI: 0.58-0.84), whereas those with a stroke history were associated with a higher risk of all-cause mortality (HR = 1.57, 95% CI: 1.15-2.16). Compared to participants with blood selenium ≥192.96 ug/L and non-stroke history, participants with both blood selenium < 192.96 ug/L and stroke history had a higher all-cause mortality risk (HR = 2.31, 95% CI: 1.62-3.29; SI = 0.713, 95% CI: 0.533-0.952). All participants with blood selenium < 192.96 ug/L and stroke history were related to higher all-cause mortality risk (HR = 1.61, 95% CI: 1.21-2.13). In males, the interaction effect of blood selenium and stroke history on all-cause mortality (HR = 2.27, 95% CI: 1.50-3.46; SI = 0.651, 95% CI: 0.430-0.986) increased twice. Conclusion: Blood selenium and stroke history have an interaction effect on all-cause mortality. Increasing selenium-rich food or supplement intake, especially for individuals with a stroke history, may improve poor prognosis.