Programming crystallization kinetics of self-assembled DNA crystals with 5-methylcytosine modification.

Self-assembled DNA crystals offer a precise chemical platform at the ångström-scale for DNA nanotechnology, holding enormous potential in material separation, catalysis, and DNA data storage. However, accurately controlling the crystallization kinetics of such DNA crystals remains challenging. Herein, we found that atomic-level 5-methylcytosine (5mC) modification can regulate the crystallization kinetics of DNA crystal by tuning the hybridization rates of DNA motifs. We discovered that by manipulating the axial and combination of 5mC modification on the sticky ends of DNA tensegrity triangle motifs, we can obtain a series of DNA crystals with controllable morphological features. Through DNA-PAINT and FRET-labeled DNA strand displacement experiments, we elucidate that atomic-level 5mC modification enhances the affinity constant of DNA hybridization at both the single-molecule and macroscopic scales. This enhancement can be harnessed for kinetic-driven control of the preferential growth direction of DNA crystals. The 5mC modification strategy can overcome the limitations of DNA sequence design imposed by limited nucleobase numbers in various DNA hybridization reactions. This strategy provides a new avenue for the manipulation of DNA crystal structure, valuable for the advancement of DNA and biomacromolecular crystallography.

Identification of multiple plasma lipids as diagnostic biomarkers of hypercholesterolemia and the underlying mechanisms based on pseudo-targeted lipidomics.

RATIONALE: Hypercholesterolemia is an important risk factor for cardiovascular diseases and death. This study performed pseudo-targeted lipidomics to identify differentially expressed plasma lipids in hypercholesterolemia, to provide a scientific basis for the diagnosis and pathogenesis of hypercholesterolemia. METHODS: Pseudo-targeted lipidomic analyses of plasma lipids from 20 patients with hypercholesterolemia and 20 normal control subjects were performed using liquid chromatography-mass spectrometry. Differentially expressed lipids were identified by principal component analysis and orthogonal partial least squares discriminant analysis. Receiver operating characteristic curves were used to identify differentially expressed lipids with high diagnostic value. The Kyoto Encyclopedia of Genes and Genomes pathway database was used to identify enriched metabolic pathways. RESULTS: We identified 13 differentially expressed lipids in hypercholesterolemia using variable importance of projection > 1 and p < 0.05 as threshold parameters. The levels of eight sphingomyelins and cholesterol sulfate were higher and those of three triacylglycerols and lysophosphatidylcholine were reduced in hypercholesterolemia. Seven differentially expressed plasma lipids showed high diagnostic value for hypercholesterolemia. Functional enrichment analyses showed that pathways related to necroptosis, sphingolipid signaling, sphingolipid metabolism, and steroid hormone biosynthesis were enriched. CONCLUSIONS: This pseudo-targeted lipidomics study demonstrated that multiple sphingomyelins and cholesterol sulfate were differentially expressed in the plasma of patients with hypercholesterolemia. We also identified seven plasma lipids, including six sphingomyelins and cholesterol sulfate, with high diagnostic value.

Genome-wide association study reveals structural chromosome variations with phenotypic effects in wheat (Triticum aestivum L.).

Structural chromosome variations (SCVs) are large-scale genomic variations that can be detected by fluorescence in situ hybridization (FISH). SCVs have played important roles in the genome evolution of wheat (Triticum aestivum L.), but little is known about their genetic effects. In this study, a total of 543 wheat accessions from the Chinese wheat mini-core collection and the Shanxi Province wheat collection were used for chromosome analysis using oligonucleotide probe multiplex FISH. A total of 139 SCVs including translocations, pericentric inversions, presence/absence variations (PAVs), and copy number variations (CNVs) in heterochromatin were identified at 230 loci. The distribution frequency of SCVs varied between ecological regions and between landraces and modern cultivars. Structural analysis using SCVs as markers clearly divided the landraces and modern cultivars into different groups. There are very clear instances illustrating alien introgression and wide application of foreign germplasms improved the chromosome diversity of Chinese modern wheat cultivars. A genome-wide association study (GWAS) identified 29 SCVs associated with 12 phenotypic traits, and five (RT4AS•4AL-1DS/1DL•1DS-4AL, Mg2A-3, Mr3B-10, Mr7B-13, and Mr4A-7) of them were further validated using a doubled haploid population and advanced sib-lines, implying the potential value of these SCVs. Importantly, the number of favored SCVs that were associated with agronomic trait improvement was significantly higher in modern cultivars compared to landraces, indicating positive selection in wheat breeding. This study demonstrates the significant effects of SCVs during wheat breeding and provides an efficient method of mining favored SCVs in wheat and other crops.

Stemness-related lncRNAs signature as a biologic prognostic model for head and neck squamous cell carcinoma.

Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are particularly important for tumor cell growth and migration, and recurrence and drug resistance, including head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to explore stemness-related lncRNAs (SRlncRNAs) that could be used for prognosis of patients with HNSCC. HNSCC RNA sequencing data and matched clinical data were obtained from TCGA database, and stem cell characteristic genes related to HNSCC mRNAsi were obtained from the online database by WGCNA analysis, respectively. Further, SRlncRNAs were obtained. Then, the prognostic model was constructed to forecast patient survival through univariate Cox regression and LASSO-Cox method based on SRlncRNAs. Kaplan-Meier, ROC and AUC were used to evaluate the predictive ability of the model. Moreover, we probed the underlying biological functions, signalling pathways and immune status hidden within differences in prognosis of patients. We explored whether the model could guide personalized treatments included immunotherapy and chemotherapy for HNSCC patients. At last, RT-qPCR was performed to analyze the expressions levels of SRlncRNAs in HNSCC cell lines. A SRlncRNAs signature was identified based on 5 SRlncRNAs (AC004943.2, AL022328.1, MIR9-3HG, AC015878.1 and FOXD2-AS1) in HNSCC. Also, risk scores were correlated with the abundance of tumor-infiltrating immune cells, whereas HNSCC-nominated chemotherapy drugs were considerably different from one another. The final finding was that these SRlncRNAs were abnormally expressed in HNSCCCS according to the results of RT-qPCR. These 5 SRlncRNAs signature, as a potential prognostic biomarker, can be utilized for personalized medicine in HNSCC patients.

Neutrophil-to-Lymphocyte ratio on admission predicts gastrointestinal bleeding in acute basal ganglia hemorrhage.

BACKGROUND: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH. METHODS: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve. RESULTS: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination. CONCLUSIONS: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage.

Iron and zinc ions, potent weapons against multidrug-resistant bacteria.

Drug-resistant bacteria are becoming an increasingly widespread problem in the clinical setting. The current pipeline of antibiotics cannot provide satisfactory options for clinicians, which brought increasing attention to the development and application of non-traditional antimicrobial substances as alternatives. Metal ions, such as iron and zinc ions, have been widely applied to inhibit pathogens through different mechanisms, including synergistic action with different metabolic enzymes, regulation of efflux pumps, and inhibition of biofilm formation. Compared with traditional metal oxide nanoparticles, iron oxide nanoparticles (IONPs) and zinc oxide nanoparticles (ZnO-NPs) display stronger bactericidal effect because of their smaller ion particle sizes and higher surface energies. The combined utilization of metal NPs (nanoparticles) and antibiotics paves a new way to enhance antimicrobial efficacy and reduce the incidence of drug resistance. In this review, we summarize the physiological roles and bactericidal mechanisms of iron and zinc ions, present the recent progress in the research on the joint use of metal NPs with different antibiotics, and highlight the promising prospects of metal NPs as antimicrobial agents for tackling multidrug-resistant bacteria.

Hexavalent chromium induces renal apoptosis and autophagy via disordering the balance of mitochondrial dynamics in rats.

The use of hexavalent chromium (Cr(VI)) in many industrial processes has resulted in serious environmental pollution problems. Cr(VI) causes organ toxicity in animals after ingestion or inhalation. However, the exact mechanism by which Cr(VI) produces kidney damage remains elusive. Herein, we investigated whether Cr(VI)-induced kidney damage is related to the disorder of mitochondrial dynamics. In this study, 28 male rats were divided into four groups and intraperitoneally injected with 0, 2, 4, and 6 mg/kg body weight potassium dichromate for 5 weeks. Experiment included analysis of renal histopathology and ultrastructure, determination of biochemical indicators, and measurement of related protein content. The results showed that Cr(VI) induced kidney injury through promotion of oxidative stress, apoptosis, and disorder of mitochondrial dynamics in a dose-dependent manner. The protein levels of the silent information regulator two ortholog 1 (Sirt1), peroxisome proliferation-activated receptor-g coactivator-1a (PGC-1a), and autophagy-related proteins were significantly decreased after Cr(VI) exposure. These findings suggest that Cr(VI) leads to the disorder of mitochondrial dynamics by inhibiting the Sirt1/PGC-1a pathway, which leads to renal apoptosis and autophagy in rats.

Chemical composition database establishment and metabolite profiling analysis of Yangyin qingfei decoction.

The chemical fingerprinting and metabolite profile in a rat plasma sample after intragastric administration of Yangyin qingfei decoction (YYQFD, 14 g/kg) were investigated. First, YYQFD was analyzed by UPLC/Q-TOF MS to establish the chemical composition database by comparing their retention behavior, accurate molecular mass and MS2 data with those of references or known compounds in the literature. In this database, 100 chemical constituents with information on retention time, molecular mass, molecular formula, MS2 data and compound name were identified, which can provide compound information for further metabolite profiling studies. Furthermore, 64 compounds including 37 prototypes and 27 metabolites were detected in the dosed rat plasma sample, and the metabolic pathways of YYQFD were hydrolyzation, hydroxylation, dehydrogenation, glucuronidation, glucosylation, sulfation and mixed modes. Among the five component herbs in the YYQFD, Glycyrrhizae Radix et Rhizome and Fritillariae Thunbergii bulbs were actively metabolized, contributing 16 and 7 metabolites, respectively. It is suggested that chemical characterization and metabolite profiling studies are valuable to elucidate the material basis of herbal preparations.

Impact of ambient PM2.5 on adverse birth outcome and potential molecular mechanism.

PM2.5 (particulate matter ≤2.5 µm in aerodynamic diameter) refers to atmospheric particulate matter (PM) with an aerodynamic diameter of equal and less than 2.5 µm that tends to be suspended for long periods of time and travel over long distances in both outdoor and indoor atmospheres. PM2.5, along with the toxic compounds attached on it, may cause a wide range of disorders. The fetus is considered to be highly susceptible to a variety of toxicants including atmospheric pollutants such as PM2.5 through prenatal exposure. To better understand the relationship between maternal exposure to PM2.5 and adverse birth outcomes for reproduction and fetus development, we studied the published data on this issue including case-control studies, cohort studies and meta-analyses studies, and summarized the basic impact of ambient particulate matter on adverse birth outcomes. Research evidence indicates that PM2.5 has a potential to induce low birth weight (LBW), preterm birth (PTB), and stillbirth. A further in-depth analysis shows that oxidative stress, DNA methylation, mitochondrial DNA (mtDNA) content alteration, and endocrine disruptions may all play an important role in PM2.5 induced adverse effects to pregnant women and fetuses. In addition, PM2.5 exposure can cause male reproductive toxicity, leading to associated adverse pregnancy outcomes.

Effects of prescription restrictive interventions on antibiotic procurement in primary care settings: a controlled interrupted time series study in China.

BACKGROUND: The overuse of antibiotics has been identified as a major challenge in regard to the rational prescription of medicines in low and middle income countries. Extensive studies on the effectiveness of persuasive interventions, such as guidelines have been undertaken. There is a dearth of research pertaining to the effects of restrictive interventions. This study aimed to evaluate the impacts of prescription restrictions in relation to types and administration routes of antibiotics on antibiotic procurement in primary care settings in China. METHODS: Data were drawn from the monthly procurement records of medicines for primary care institutions in Hubei province over a 31-month period from May 2011 to November 2013. We analyzed the monthly procurement volume and costs of antibiotics. Interrupted time series analyses with a difference-in-difference approach were performed to evaluate the effect of the restrictive intervention (started in August 2012) on antibiotic procurement in comparison with those for cardiovascular conditions. Sensitivity tests were performed by replacing outliers using a simple linear interpolation technique. RESULTS: Over the entire study period, antibiotics accounted for 33.65% of the total costs of medicines procured for primary care institutions: mostly non-restricted antibiotics (86.03%) and antibiotics administered through parenteral routes (79.59%). On average, 17.14 million defined daily doses (DDDs) of antibiotics were procured per month, with the majority (93.09%) for non-restricted antibiotics and over half (52.38%) for parenteral administered antibiotics. The restrictive intervention was associated with a decline in the secular trend of costs for non-restricted oral antibiotics (- 0.36 million Yuan per month, p = 0.029), and for parenteral administered restricted antibiotics (- 0.28 million Yuan per month, p = 0.019), as well as a decline in the secular trend of procurement volume for parenteral administered non-restricted antibiotics (- 0.038 million DDDs per month, p = 0.05). CONCLUSIONS: Restrictive interventions are effective in reducing the procurement of antibiotics. However, the effect size is relatively small and antibiotic consumptions remain high, especially parenteral administered antibiotics.

Fructus Ligustri Lucidi modulates estrogen receptor expression with no uterotrophic effect in ovariectomized rats.

BACKGROUND: Accumulating evidence suggests that Fructus Ligustri Lucidi (FLL) plays a beneficial role in preventing the development of osteoporosis. However, the effects of FLL on estrogen receptor (ER) α and ERß expressions remain unknown. Therefore, in the current study we attempted to probe into the effects of FLL on ERα and ERß expressions in femurs, tibias and uteri of ovariectomized (OVX) rats. METHODS: The OVX rats were orally administrated with FLL water extract (3.5 g/kg/day) for 12 weeks. The uteri, femurs, tibias and serum were harvested from rats. The serum levels of estrogen (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by ELISA. The expressions of ERα and ERß in the femurs and tibias as well as uteri were analysed by western blot and immunohistochemical staining. RESULTS: FLL treatment did not increase uterus relative weight in OVX rats. Further, FLL treatment increased ERα expression in the femurs and tibias, and enhanced ERß expression in the uteri of OVX rats. However, the resulted expression of ERα was stronger than that of ERß in OVX rats in response to FLL treatment. Meanwhile, administration with FLL to OVX rats increased FSH and LH but did not increase E2 level in the serum. CONCLUSION: FLL treatment shows tissue selection on ERα and ERß expressions in the femurs and tibias as well as uteri of OVX rats without uterotrophic effect, which may offer the scientific evidence of the efficiency and safety of its clinical application.

General practitioners' perceptions of public reporting of institution and individual medicine prescribing data.

BACKGROUND: Public reporting of institution- and individual-level performance data has recently become a popular topic in the health care field. This study (1) evaluated the perceptions of general practitioners on the public reporting of institutional and individual medicine prescribing data in primary care institutions, and (2) compared the difference among the perceptions of general practitioners on the dimensions of necessity, methodological rigor, and impact of public reporting medicine prescribing data. METHODS: We conducted a survey in 10 primary care institutions in Q city, Hubei province. General practitioners who hold prescribing license were eligible for this study; we surveyed all eligible general practitioners in July 2014. The survey instrument was developed based on previous studies and expert opinions. Paired t-test or nonparametric test was used to evaluate the difference in perceptions between the institutional and individual medicine prescribing data reporting. An analysis of variance test was used to analyze the score differences among the three dimensions (i.e., necessity, methodological rigor, and impact). RESULTS: A total of 154 general practitioners were surveyed in this study. No significant difference in the perceptions of general practitioners was observed between the institution- and individual-level medicine prescribing data reporting (p > 0.05). General practitioners have significantly different perceptions on the three dimensions of the institution- and individual-level data reporting (p < 0.05). Methodological rigor obtained the lowest score. Regarding the strategies to facilitate the medicine prescribing data reporting, over 80 % of general practitioners selected the items that disclose process measures and not outcome measures, as well as educate patients on data interpretation. CONCLUSION: The perceptions of general practitioners between institution- and individual-level data reporting have no significant difference. General practitioners place their utmost concern on public reporting on the methodological rigor. Processing measures and patient education to improve the efficiency of public reporting require substantial attention.

Curcumin treatment suppresses CCR7 expression and the differentiation and migration of human circulating fibrocytes.

BACKGROUND/AIM: Recent studies have demonstrated that circulating fibrocytes contribute to the formation and development of fibrosis. Curcumin, a polyphenolic compound isolated from turmeric, has been shown to have anti-fibrotic effects in various organs. We and others have demonstrated that curcumin beneficially affects the development of fibrosis. However the effect of curcumin on circulating fibrocytes has not been reported. METHODS: Human circulating fibrocytes were isolated from leukocyte concentrates of healthy human donors and identified based on the expression of CD34, CD45, collagen I (COLI), and chemokine receptor CCR7 (CCR7) via flow cytometry. Cell Counting Kit-8 was used to evaluate cell viability. The effect of curcumin on the differentiation and migration of human circulating fibrocytes was evaluated by immunofluorescence staining, flow cytometry and a transwell migration assay. Transforming growth factor (TGF)-ß1 secretion was examined by ELISA. RESULTS: Curcumin treatment (72 h; 20 µM) significantly decreased the expression of COL I, α-SMA and CCR7, as well as TGF-ßl secretion, in human circulating fibrocytes. The inhibitory effect of curcumin on the differentiation and migration of human circulating fibrocytes is likely via regulating the CCR7/CCL21 signaling pathway, in particular by reducing CCR7 expression. These observed effects may be beneficial in resolving fibrosis by suppressing TGF-ß1 secretion. CONCLUSION: Our results suggest that curcumin has the potential to suppress the differentiation and migration of circulating fibrocytes, which would provide new explanation for curcumin's application in the development of fibrosis in various organs.

Effects of transparent online open procurement on prices, volumes, and costs of medicines: an interrupted time series study in Ningxia, China.

Objectives: To assess the effects of the transparent online open procurement arrangement on the prices, volumes, and costs of medicines in Ningxia, China. Methods: Data were extracted from the Ningxia pharmaceutical procurement platform, covering 16 months of purchase orders (December 2019 to March 2021) prior to the implementation of the transparent online open procurement policy and 20 months of purchase orders after the implementation of the policy (April 2021 to November 2022). Interrupted time series (ITS) analysis was performed to evaluate the effects of the transparent online open procurement policy on the prices, volumes, and total costs of the purchase orders. Results: After implementation of the transparent online open procurement policy, the average price of purchased medicines showed a declining trend by 0.012 Yuan per month, while the total volume of purchase orders declined at a rate by 1.741 million per month measured by the smallest formulation units and the total costs of the purchase orders decreased at a rate by 5.525 million Yuan per month. Conclusion: The transparent online open procurement policy resulted in reduced prices, lowered volumes, and lowered total costs of purchased orders of medicines.

Policy text analysis of antimicrobial resistance governance in China: A focus on national-level policies.

OBJECTIVE: To explore the structure and characteristics of China's national policies regarding antimicrobial resistance (AMR) governance. METHOD: This research constitutes a quantitative content analysis of AMR policies issued by the central government from 2004 to 2023. A systematic search identified 112 policy documents, which were analysed using a three-dimensional framework. This framework included policy objectives, policy instruments (The supply-focused instrument aims to promote rational and prudent antibiotic prescriptions. The demand-focused instrument affects consumer use of antibiotics, either directly or indirectly. The environment-focused instrument provides a favourable and systematic policy environment for the prudent use of antibiotics.) and policy evolvement. Sub-themes under the framework were identified through a deductive process, followed by descriptions of frequency distributions of the sub-themes and categories. RESULTS: The majority of policy documents originated from individual governmental departments, with only 8 (7.14%) being jointly issued. The National Health Commission (NHC) remained the predominant policy maker, issuing 56 (48.21%) policies. A clear preference emerged for utilizing environment-focused policy instruments (69.70%), compared with the demand-focused (18.45%) and supply-focused (11.85%) instruments. 'Optimizing the use of antimicrobial medicines' ranked on top of the policy objectives, with 185 (31.25%) citations extracted across 74 (30.58%) policy documents. In addition to increasing numbers of policies over the three stages (2004-2011, 2012-2015, 2016-2023) of development, the use of various instruments became more comprehensive and balanced in the third stage. CONCLUSIONS: AMR governance has become increasingly comprehensive in China, despite a deficit in inter-sectoral collaborations. A whole-of-government approach is required to maximize the value of various policy initiatives.

Preference of primary care patients for home-based healthcare and support services: a discrete choice experiment in China.

Importance: This research, utilizing discrete choice experiments, examines the preferences and willingness to pay for home-based healthcare and support services among residents in China, a country grappling with severe aging population, an area often underexplored in international scholarship. Objectives: This study aims to solicit the preferences of primary care patients for home-based healthcare and support services in China. Design setting and participants: A discrete choice experiment (DCE) was conducted on 312 primary care patients recruited from 13 community health centers in Wuhan and Kunming between January and May 2023. The experimental choice sets were generated using NGene, covering five attributes: Scope of services, health professionals, institutions, insurance reimbursements, and visiting fees. Main outcomes and measures: The choice sets were further divided into three blocks, and each participant was asked to complete one block containing 12 choice tasks. Mixed logit models were established to estimate the relevant importance coefficients of and willingness to pay for different choices, while Latent Class Logit (LCL) modeling was conducted to capture possible preferences heterogeneity. Results: The relevant importance of the scope of services reached 67.33%, compared with 19.84% for service institutions and 12.42% for health professionals. Overall, respondents preferred physician-led diagnostic and treatment services. LCL categorized the respondents into three groups: Group one (60.20%) was most concerned about the scope of services, prioritizing disease diagnosis and treatment over preventive care and mental health, while group two (16.60%) was most concerned about care providers (hospitals and medical doctors were preferred), and group three (23.20%) was most concerned about financial burdens. Conclusion: Primary care patients prefer physical health and medical interventions for home-based healthcare and support services. However, heterogeneity in preferences is evident, indicating potential disparities in healthcare and support at home services in China.

Alterations in cortical volume and complexity in Parkinson's disease with depression.

AIMS: The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. METHODS: A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores. RESULTS: PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. CONCLUSION: Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.

Identification of key sensory and chemical factors determining flavor quality of Xinyu mandarin during ripening and storage.

Xinyu mandarin is popular for its good flavor, but its flavor deteriorates during postharvest storage. To better understand the underlying basis of this change, the dynamics of the sensory profiles were investigated throughout fruit ripening and storage. Sweetness and sourness, determined especially by sucrose and citric acid content, were identified as the key sensory factors in flavor establishment during ripening, but not in flavor deterioration during storage. Postharvest flavor deterioration is mainly attributed to the reduction of retronasal aroma and the development of off-flavor. Furthermore, sugars, acids and volatile compounds were analyzed. Among the 101 detected volatile compounds, 10 changed significantly during the ripening process. The concentrations of 15 volatile components decreased during late postharvest storage, among which α-pinene and d-limonene were likely to play key roles in the reduction of aroma. Three volatile compounds were found to increase during storage, associated with off-flavor development.

Survival analysis in pT1-3 and paracolic lymph-node invasion colorectal cancer: the prognostic role of positive paracolic lymph-node ratio for adjuvant chemotherapy.

PURPOSE: Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. METHODS: Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan-Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. RESULTS: We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74%) and DFS (87.65 vs. 90.96%) between stage III patients with pT1-3N + (P-LNR ≤ 0.15)M0 and those with pT1-3N0M0. Further analysis demonstrated that CRC patients with pT1-3N + (P-LNR ≤ 0.15)M0 were less likely to benefit from 8 cycles of CAPOX or FOLFOX chemotherapy and suffered fewer adverse events from declining chemotherapy. Comparing with 0-4 cycles versus 8 cycles, the overall survival rates were 91.35 versus 90.19% (P = 0.79), and with a DFS of 87.50 versus 88.24% (P = 0.49), the duration of adjuvant chemotherapy was not an independent risk factor for patients with pT1-3N + (P-LNR ≤ 0.15)M0 (HR: 0.70, 95% CI 0.90-1.30, P = 0.42). CONCLUSION: The concept of P-LNR we proposed might have a high clinical application value and accurately enable clinicians to screen out specific CRC patients who decline or prefer limited chemotherapy. TRIAL REGISTRY: The clinical trial registration number: ChiCTR2300076883.

Exploring brain asymmetry in early-stage Parkinson's disease through functional and structural MRI.

OBJECTIVE: This study explores the correlation between asymmetrical brain functional activity, gray matter asymmetry, and the severity of early-stage Parkinson's disease (PD). METHODS: Ninety-three early-stage PD patients (ePD, H-Y stages 1-2.5) were recruited, divided into 47 mild (ePD-mild, H-Y stages 1-1.5) and 46 moderate (ePD-moderate, H-Y stages 2-2.5) cases, alongside 43 matched healthy controls (HCs). The study employed the Hoehn and Yahr (H-Y) staging system for disease severity assessment and utilized voxel-mirrored homotopic connectivity (VMHC) for analyzing brain functional activity asymmetry. Asymmetry voxel-based morphometry analysis (VBM) was applied to evaluate gray matter asymmetry. RESULTS: The study found that, relative to HCs, both PD subgroups demonstrated reduced VMHC values in regions including the amygdala, putamen, inferior and middle temporal gyrus, and cerebellum Crus I. The ePD-moderate group also showed decreased VMHC in additional regions such as the postcentral gyrus, lingual gyrus, and superior frontal gyrus, with notably lower VMHC in the superior frontal gyrus compared to the ePD-mild group. A negative correlation was observed between the mean VMHC values in the superior frontal gyrus and H-Y stages, UPDRS, and UPDRS-III scores. No significant asymmetry in gray matter was detected. CONCLUSIONS: Asymmetrical brain functional activity is a significant characteristic of PD, which exacerbates as the disease severity increases, resembling the dissemination of Lewy bodies across the PD neurological framework. VMHC emerges as a potent tool for characterizing disease severity in early-stage PD.