Novel insights into the glucose metabolic alterations of freshwater snails: a pathway to molluscicide innovation and snail control strategies.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Assessing the impact of specific PM2.5-Bound metallic elements on asthma emergency department visits: A case-crossover study in Taiwan.

OBJECTIVES: This study aims to assess the specific PM2.5-bound metallic elements that contribute to asthma emergency department visits by using a case-crossover study design. METHODS: This study analyzed data from 11,410 asthma emergency department visits as case group and 22,820 non-asthma onset dates occurring one week and two weeks preceding the case day as controls from 2017 to 2020. PM2.5 monitoring data and 35 PM.2.5-bound metallic elements from six different regions in Taiwan were collected. Conditional logistic regression models were used to assess the relationship between asthma and PM2.5-bound metallic elements. RESULTS: Our investigation revealed a statistically significant risk of asthma emergency department visits associated with PM2.5 exposure at lag 0, 1, 2, and 3 during autumn. Additionally, PM2.5-bound hafnium (Hf), thallium (Tl), rubidium (Rb), and aluminum (Al) exhibited a consistently significant positive correlation with asthma emergency department visits at lags 1, 2, and 3. In stratified analyses by area, age, and sex, PM2.5-bound Hf showed a significant and consistent correlation. CONCLUSIONS: This study provides evidence of PM2.5-bound metallic elements effects in asthma exacerbations, particularly for Hf. It emphasizes the importance of understanding the origins of these metallic elements and pursuing emission reductions to mitigate regional health risks.

Neural Interface-Based Motor Neuroprosthesis in Poststroke Upper Limb Neurorehabilitation: An Individual Patient Data Meta-analysis.

OBJECTIVE: To determine the efficacy of neural interface-based neurorehabilitation, including brain-computer interface, through conventional and individual patient data (IPD) meta-analysis and to assess clinical parameters associated with positive response to neural interface-based neurorehabilitation. DATA SOURCES: PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. STUDY SELECTION: Studies using neural interface-controlled physical effectors (functional electrical stimulation and/or powered exoskeletons) and reported Fugl-Meyer Assessment-upper-extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. DATA EXTRACTION: Changes in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. DATA SYNTHESIS: Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE scores increased by a mean of 5.23 (95% confidence interval [CI]: 3.85-6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 vs ≤4 weeks. On IPD analysis, the mean time-to-improvement above minimal clinically important difference (MCID) was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41%-70%). Patients with severe impairment (P=.042) and age >50 years (P=.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (hazard ratio [HR] 0.15, P=.08 and HR 0.47, P=.06, respectively). CONCLUSION: Neural interface-based motor rehabilitation resulted in significant, although modest, reductions in poststroke impairment and should be considered for wider applications in stroke neurorehabilitation.

Potential Application Prospects of Biomolecule-Modified Two-Dimensional Chiral Nanomaterials in Biomedicine.

Chirality, one of the most fundamental properties of natural molecules, plays a significant role in biochemical reactions. Nanomaterials with chiral characteristics have superior properties, such as catalytic properties, optoelectronic properties, and photothermal properties, which have significant potential for specific applications in nanomedicine. Biomolecular modifications such as nucleic acids, peptides, proteins, and polysaccharides are sources of chirality for nanomaterials with great potential for application in addition to intrinsic chirality, artificial macromolecules, and metals. Two-dimensional (2D) nanomaterials, as opposed to other dimensions, due to proper surface area, extensive modification sites, drug loading potential, and simplicity of preparation, are prepared and utilized in diagnostic applications, drug delivery research, and tumor therapy. Current advanced studies on 2D chiral nanomaterials for biomedicine are focused on novel chiral development, structural control, and materials sustainability applications. However, despite the advances in biomedical research, chiral 2D nanomaterials still confront challenges such as the difficulty of synthesis, quality control, batch preparation, chiral stability, and chiral recognition and selectivity. This review aims to provide a comprehensive overview of the origins, synthesis, applications, and challenges of 2D chiral nanomaterials with biomolecules as cargo and chiral modifications and highlight their potential roles in biomedicine.

Longitudinal assessment of oxidative stress markers and their relationship with exposure to PM2.5 and its bound metals in healthy participants.

OBJECTIVE: Exposure to ambient PM2.5 and its bound metals poses a risk to health and disease, via, in part, oxidative stress response. A variety of oxidative stress markers have been used as markers of response, but their relevance to environmental exposure remains to be established. We evaluated, longitudinally, a battery of oxidative stress markers and their relationship with the exposure of PM2.5 and its bound metals in a panel of healthy participants. MATERIAL AND METHODS: Levels of residence- and personal-based ambient air PM2.5 and its bound metals, as well as of lung function parameters, were assessed in a total of 58 questionnaire-administered healthy never smoker participants (male, 39.7%). Levels of urinary oxidative stress markers, including Nε-(hexanoyl)-lysine (HEL; an early lipid peroxidation product), 4-hydroxynonenal (4-HNE), N7-methylguanine (N7-meG), and 8-hydroxy-2-deoxyguanosine (8-OHdG), plasma antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GPx), and urinary metals were measured by ELISA, LC-MS, and ICP-MS, respectively. The results of three repeated measurements at two-month intervals were analyzed using the Generalized Estimating Equation (GEE). RESULTS: After adjusting for confounders, residence- and personal-based PM2.5 levels were positively associated with HEL (ß = 0.22 and 0.18) and N7-meG (ß = 0.39 and 0.13). Significant correlations were observed between personal air PM2.5-Pb and urinary Pb with HEL (ß = 0.08 and 0.26). While FVC, FEV1, FEV1/FVC, MMF, and PEFR predicted% were normal, a negative interaction (pollutant*time, P < 0.05) was noted for PM2.5-V, Mn, Co, Ni, Zn, As, and Pb. Additionally, a negative interaction was found for N7-meG (ß = -21.35, -18.77, -23.86) and SOD (ß = -26.56, -26.18, -16.48) with FEV1, FVC, and PEFR predicted%, respectively. CONCLUSION: These findings emphasize potential links between environmental exposure, internal dose, and health effects, thereby offering valuable markers for future research on metal exposure, oxidative stress, and health outcomes.

Astrocyte-derived lactoferrin reduces ß-amyloid burden by promoting the interaction between p38 kinase and PP2A phosphatase in male APP/PS1 transgenic mice.

BACKGROUND AND PURPOSE: Overexpression of astrocytic lactoferrin (Lf) was observed in the brain of Alzheimer's disease (AD) patients, whereas the role of astrocytic Lf in AD progression remains unexplored. In this study, we aimed to evaluate the effects of astrocytic Lf on AD progression. EXPERIMENTAL APPROACH: Male APP/PS1 mice with astrocytes overexpressing human Lf were developed to evaluate the effects of astrocytic Lf on AD progression. N2a-sw cells also were employed to further uncover the mechanism of astrocytic Lf on ß-amyloid (Aß) production. KEY RESULTS: Astrocytic Lf overexpression increased protein phosphatase 2A (PP2A) activity and reduced amyloid precursor protein (APP) phosphorylation, Aß burden and tau hyperphosphorylation in APP/PS1 mice. Mechanistically, astrocytic Lf overexpression promoted the uptake of astrocytic Lf into neurons in APP/PS1 mice, and conditional medium from astrocytes overexpressing Lf inhibited p-APP (Thr668) expression in N2a-sw cells. Furthermore, recombinant human Lf (hLf) significantly enhanced PP2A activity and inhibited p-APP expression, whereas inhibition of p38 or PP2A activities abrogated the hLf-induced p-APP down-regulation in N2a-sw cells. Additionally, hLf promoted the interaction of p38 and PP2A via p38 activation, thereby enhancing PP2A activity, and low-density lipoprotein receptor-related protein 1 (LRP1) knockdown significantly reversed the hLf-induced p38 activation and p-APP down-regulation. CONCLUSIONS AND IMPLICATIONS: Our data suggested that astrocytic Lf promoted neuronal p38 activation, via targeting to LRP1, subsequently promoting p38 binding to PP2A to enhance PP2A enzyme activity, which finally inhibited Aß production via APP dephosphorylation. In conclusion, promoting astrocytic Lf expression may be a potential strategy against AD. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

From zinc homeostasis to disease progression: Unveiling the neurodegenerative puzzle.

Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.

Cancer risks in a population-based study of agricultural workers: results from the Taiwan's Farmers and Health Cohort study.

OBJECTIVE: The purpose of this study was to assess cancer risk among agricultural workers compared to the general population. METHODS: The study utilized data from Farmers' Health Insurance (FHI) in Taiwan, which enrolled agricultural workers (N=1 175 149). The enrolled workers were matched to a general population (N=1 175 149) of the same age, gender, township, and enrollment year. The study population was linked to the National Cancer Registry to identify new cancer cases between 2000 and 2018. The Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval for outcomes. RESULTS: During the study period, 136 913 new cancers among agricultural workers were identified. The study found that male farmers had an increased cancer risk, including lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma (NHL), oral cancer, lip cancer, esophagus cancer, rectum and rectosigmoid junction cancer, liver and intrahepatic bile duct cancer, lung cancer, trachea and bronchi cancer, and other non-melanoma skin cancer, even when considering the latency period. Female farmers had an elevated risk of multiple myeloma and other non-melanoma skin cancer. Moreover, only lymphoma, NHL, other lymphoid, and multiple myeloma, were both found to occur at different insurance periods. CONCLUSIONS: This study provides farmer cancer patterns and risk, adding to the evidence that farmers are at increased risk of certain types of cancer, especially for hematological cancers. As exposure varies by farm operation type, individual farmer exposure may vary widely. Further understanding of the complex relationship between occupational exposure, environmental factors, and lifestyle factors is needed.

The predictive role of platelet count for bleeding in patients with hepatitis B virus and hepatitis C virus infection.

The impact of platelet count on bleeding in hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients is unclear. We aimed to evaluate the relationship between platelet count and bleeding in patients with viral hepatitis. We selected patients with HBV and HCV infection. All esophagogastroduodenoscopy, colonoscopy, and brain imaging reports were reviewed to document upper gastrointestinal bleeding (UGIB), lower gastrointestinal bleeding (LGIB), and central nervous system bleeding (CNSB), respectively. We analyzed risk factors for first bleeding events by using Cox proportional hazards models. Incidence rate ratios (IRRs) were used to compare bleeding incidences between viral types and platelet levels. A total of 2522 HCV and 2405 HBV patients were enrolled. The HCV-to-HBV IRRs of UGIB, LGIB, and CNSB were significant at 1.797, 2.255, and 2.071, respectively. The common risk factors in both groups were thrombocytopenia, hypoalbuminemia, high alkaline phosphatase level, and cirrhosis for UGIB, whereas thrombocytopenia and hypoalbuminemia for LGIB. Hypoalbuminemia was the only risk for CNSB. After adjusting platelet count, the higher bleeding rates in the HCV patients diminished. Using a reference platelet count less than 100 x 10 9 /l, bleeding risk elevated at platelet count less than 70 x 10 9 /l and less than 40 x 10 9 /l for UGIB and LGIB in the HCV patients, respectively, compared with less than 60 x 10 9 /l for UGIB in the HBV patients. The incidence of CNSB was not related to platelet levels. HCV patients had a higher risk for major bleeding. Thrombocytopenia was a significant predictor. Monitoring and management of thrombocytopenia in addition to cirrhotic status was important in these patients.

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway.

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

Efficacy of Baishao Luoshi decoction on synaptic plasticity in rats with post stroke spasticity.

OBJECTIVE: To evaluate the efficacy of Baishao Luoshi decoction (, BD) on synaptic plasticity in rats with post stroke spasticity (PSS), and to study the mechanism behind the action. METHODS: The PSS model of rat was established by middle cerebral artery occlusion (MCAO). The neurological deficit symptoms were evaluated by modified neurological deficit score (mNSS). Muscle tension were evaluated by Modified Ashworth score (MAS). Transmission electron microscopy (TEM) was used to observe the synaptic ultrastructure. The expression of synaptic plasticity-related protein brain derived neurotrophic factor (BDNF), growth associated protein-43 (GAP43), synaptophysin (p38) and microtubule-associated protein 2 (MAP2) in the brain tissue around the infarct were detected by Western blotting. RESULTS: We found that mNSS were significantly improved and limb spasticity was ameliorated treated by BD. The thickness of postsynaptic density and the synaptic curvature increased significantly. The expression of synaptic plasticity-related protein BDNF, GAP43, p38, MAP2 in the brain tissue around the infarct were raised remarkably after treated by BD. CONCLUSIONS: Alleviating PSS by BD may be related to rescuing the synaptic plasticity, which provides a probable new therapeutic method for PSS.

Characteristics, origin, and processing of Poria in Qing Dynasty Palace:evidence of both historical relics and documents / 中国中药杂志

Poria(Fu Ling) is a bulk traditional Chinese medicine(TCM)with a long history and complex varieties. The royal medical records of the Qing Dynasty include multiple medicinal materials of Fu Ling, such as Bai Fu Ling(white Poria), Chi Fu Ling(rubra Poria), and Zhu Fu Ling(Poria processed with cinnabaris). The Palace Museum preserves 6 kinds of specimens including Fu Ling Ge(dried Poria), Bai Fu Ling, Chi Fu Ling, Zhu Fu Ling, Bai Fu Shen(white Poria cum Radix Pini), and Fu Shen Mu(Poria cum Radix Pini). After trait identification and textual research, we found that Fu Ling Ge was an intact sclerotium, which was processed into Fu Ling Pi(Poriae Cutis), Bai Fu Ling and other medicinal materials in the Palace. The Fu Ling in the Qing Dynasty Pa-lace was mainly from the tribute paid of the officials in Yunnan-Guizhou region. The tribute situation was stable in the whole Qing Dynasty, and changed in the late Qing Dynasty. The cultural relics of Fu Ling in the Qing Dynasty Palace confirm with the archival documents such as the royal medical records and herbal medicine books, providing precious historical materials for understanding Fu Ling in the Qing Dynasty and a basis for the restoration of the processing of the Fu Ling in the Qing Dynasty Palace.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Quality of life and symptom distress after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/ HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL). AIM: To investigate early perioperative QoL after CRS/HIPEC, which has not been discussed in Taiwan. METHODS: This single institution, observational cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 mo after CRS/HIPEC (S3). RESULTS: Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results. CONCLUSION: QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

The Effect of Polysaccharides on Preventing Proteins and Cholesterol from Being Adsorbed on the Surface of Orthokeratology Lenses.

The adsorption of tear film compositions such as proteins and lipids on the orthokeratology lenses often lead to infection or corneal damage. In order to investigate whether polysaccharides could prevent tear compositions from being adsorbed on the lens, alginic acid and lambda-carrageenan were added into artificial tear solution. By measuring daily adsorption of cholesterol, lysozyme, and albumin, our results showed that polysaccharides could weakly prevent cholesterol adsorption. In addition, polysaccharides could also reduce albumin deposition over time. Although the effect of polysaccharides on lysozyme adsorption was distinct depending on the concentrations of polysaccharides, the overall results demonstrated that polysaccharides could decrease protein deposition over time. Our results provided an in vitro evidence that polysaccharides may be applied as coating materials on the lens or as the composition of artificial tear solutions or eyedrops, in order to prevent adsorption of tear film compositions that may lead to a reduced incidence of infection or corneal damage for orthokeratology lens wearers.

Label-free and de-conjugation-free workflow to simultaneously quantify trace amount of free/conjugated and protein-bound estrogen metabolites in human serum.

Different chemical forms of sex hormones including free/conjugated metabolites as well as their protein/DNA adducts in human serum are a panel of important indicators of health conditions. It is, however, hard to quantify all species simultaneously due to the lack of general extraction, derivatization, and de-conjugation methods. Here we developed a label-free and de-conjugation-free workflow to quantify 11 free/conjugated estrogen metabolites including depurinating DNA and protein adduct forms of 4-hydroxyestradiol (4OHE2) in human serum. Acetonitrile acts as an excellent solvent to purify adducted and non-adducted human serum albumin (HSA) by precipitation as well as to extract free/conjugated metabolites and depurinating DNA adducts from the supernatant by salting-out effect. The adduction level of 4OHE2 on HSA was determined by proteomics; free/conjugated metabolites were quantified by a newly developed microflow liquid chromatography (microflow LC)-nanoelectrospray ionization (nanoESI)-multiple reaction monitoring (MRM) method with high reproducibility (7-22% RSD, n > 3) and sub-picogram levels (0.6-20 pg/mL) of quantification limits (S/N = 8) by using non-pulled capillary as nano-ESI emitter. This workflow was demonstrated to reveal endogenous adduction level of 4OHE2 on HSA as well as circulation levels of free/conjugated metabolites in clinical samples. 4OHE2 in human serum were solely detected as protein-bound form, indicating the merit of such integrated platform covering unstable or active metabolites. Compared to traditional methods using labeling or de-conjugation reaction, this workflow is much simplier, more sensitive, and more specific. Moreover, it can be widely applied in omics to concurrently access various bio-transformed known and un-known markers or drugs.

Lipid Droplets in Lung Cancers Are Crucial for the Cell Growth and Starvation Survival.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.