Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Flexible Hydrazone-Linked Metal-Covalent Organic Frameworks with Copper Clusters for Efficient Electrocatalytic Oxygen Evolution Reaction.

Despite the challenges associated with the synthesis of flexible metal-covalent organic frameworks (MCOFs), these offer the unique advantage of maximizing the atomic utilization efficiency. However, the construction of flexible MCOFs with flexible building units or linkages has rarely been reported. In this study, novel flexible MCOFs are constructed using flexible building blocks and copper clusters with hydrazone linkages. The heterometallic frameworks (Cu, Co) are prepared through the hydrazone linkage coordination method and evaluated as catalysts for the oxygen evolution reaction (OER). Owing to the spatial separation and functional cooperation of the heterometallic MCOF catalysts, the as-synthesized MCOFs exhibited outstanding catalytic activities with an overpotential of 268.8 mV at 10 mA cm-2 for the OER in 1 M KOH, which is superior to those of the reported covalent organic frameworks (COFs)-based OER catalysts. Theoretical calculations further elucidated the synergistic effect of heterometallic active sites within the linkages and frameworks, contributing to the enhanced OER activity. This study thus introduces a novel approach to the fundamental design of flexible MCOF catalysts for the OER, emphasizing their enhanced atomic utilization efficiency.

Preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy for esophageal squamous cell carcinoma associates with postoperative pulmonary complications following radical esophagectomy.

OBJECTIVES: Esophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy. METHODS: We retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival. RESULTS: Postoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively. Preoperative neutrophil-to-lymphocyte ratio was not associated with the oncological stratification such as pathological T classification, pathological N classification, and pathological AJCC stage. The 3-year overall survival rates were 70% and 34% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0026). The 3-year disease-free survival rates were 57% and 29% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0055). The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 was independently associated with more pulmonary complications, inferior overall survival, and worse disease-free survival. CONCLUSIONS: Elevated preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy is independently associated with higher pulmonary complication rate following radical esophagectomy and poor prognosis in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy. Preoperative neutrophil-to-lymphocyte ratio is routinely available in clinical practice and our findings suggest it can be used as a predictor for pulmonary complications after esophagectomy in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy.

Surface Proteins of Bifidobacterium Bifidum DNG6 Growing in 2'-FL Alleviating LPS-Induced Intestinal Barrier Injury in vitro.

Human milk oligosaccharides (HMOs) promote the growth and adhesion of bifidobacteria, thus exerting multiple biological functions on intestinal epithelial cells. Bacterial surface proteins play an important role in bacterial-host intestinal epithelial interactions. In this study, we aim to investigate the effects of surface proteins extracted from Bifidobacterium bifidum DNG6 (B. bifidum DNG6) consuming 2'-fucosyllactose (2'-FL) on Caco-2 cells monolayer barrier injury induced by lipopolysaccharide, compared with lactose (Lac) and galacto-oligosaccharides (GOS). Our results indicated that 2'-FL may promote the surface proteins of B. bifidum DNG6 to improve intestinal barrier injury by positively regulating the NF-κB signaling pathway, reducing inflammation(TNF-α reduced to 50.34%, IL-6 reduced to 22.83%, IL-1ß reduced to 37.91%, and IL-10 increased to 63.47%)and strengthening tight junction (ZO-1 2.39 times, Claudin-1 2.79 times, and Occludin 4.70 times). The findings of this study indicate that 2'-FL can further regulate intestinal barrier damage by promoting the alteration of B. bifidum DNG6 surface protein. The findings of this research will also provide theoretical support for the development of synbiotic formulations.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Phenolic acids from medicinal and edible homologous plants: a potential anti-inflammatory agent for inflammatory diseases.

Inflammation has been shown to trigger a wide range of chronic diseases, particularly inflammatory diseases. As a result, the focus of research has been on anti-inflammatory drugs and foods. In recent years, the field of medicinal and edible homology (MEH) has developed rapidly in both medical and food sciences, with 95% of MEH being associated with plants. Phenolic acids are a crucial group of natural bioactive substances found in medicinal and edible homologous plants (MEHPs). Their anti-inflammatory activity is significant as they play a vital role in treating several inflammatory diseases. These compounds possess enormous potential for developing anti-inflammatory drugs and functional foods. However, their development is far from satisfactory due to their diverse structure and intricate anti-inflammatory mechanisms. In this review, we summarize the various types, structures, and distribution of MEHP phenolic acids that have been identified as of 2023. We also analyze their anti-inflammatory activity and molecular mechanisms in inflammatory diseases through NF-κB, MAPK, NLRP3, Nrf2, TLRs, and IL-17 pathways. Additionally, we investigate their impact on regulating the composition of the gut microbiota and immune responses. This analysis lays the groundwork for further exploration of the anti-inflammatory structure-activity relationship of MEHP phenolic acids, aiming to inspire structural optimization and deepen our understanding of their mechanism, and provides valuable insights for future research and development in this field.

Pharmacological actions of the bioactive compounds of Epimedium on the male reproductive system: current status and future perspective.

ABSTRACT: Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.

Attitude and utilization of ChatGPT among registered nurses: A cross-sectional study.

AIM: This study explores the influencing factors of attitudes and behaviors toward use of ChatGPT based on the Technology Acceptance Model among registered nurses in Taiwan. BACKGROUND: The complexity of medical services and nursing shortages increases workloads. ChatGPT swiftly answers medical questions, provides clinical guidelines, and assists with patient information management, thereby improving nursing efficiency. INTRODUCTION: To facilitate the development of effective ChatGPT training programs, it is essential to examine registered nurses' attitudes toward and utilization of ChatGPT across diverse workplace settings. METHODS: An anonymous online survey was used to collect data from over 1000 registered nurses recruited through social media platforms between November 2023 and January 2024. Descriptive statistics and multiple linear regression analyses were conducted for data analysis. RESULTS: Among respondents, some were unfamiliar with ChatGPT, while others had used it before, with higher usage among males, higher-educated individuals, experienced nurses, and supervisors. Gender and work settings influenced perceived risks, and those familiar with ChatGPT recognized its social impact. Perceived risk and usefulness significantly influenced its adoption. DISCUSSION: Nurse attitudes to ChatGPT vary based on gender, education, experience, and role. Positive perceptions emphasize its usefulness, while risk concerns affect adoption. The insignificant role of perceived ease of use highlights ChatGPT's user-friendly nature. CONCLUSION: Over half of the surveyed nurses had used or were familiar with ChatGPT and showed positive attitudes toward its use. Establishing rigorous guidelines to enhance their interaction with ChatGPT is crucial for future training. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers should understand registered nurses' attitudes toward ChatGPT and integrate it into in-service education with tailored support and training, including appropriate prompt formulation and advanced decision-making, to prevent misuse.

Recurrence in isolated distal DVT after anticoagulation: a systematic review and meta-analysis of axial and muscular venous thrombosis.

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

Zinc oxide nanoparticles induces cell death and consequently leading to incomplete neural tube closure through oxidative stress during embryogenesis.

The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn2+ they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn2+ played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.

Renal protective effect of metformin in type 2 diabetes patients.

BACKGROUND: Inhibiting the development and progression of diabetic kidney disease (DKD) is an important issue, but the renoprotective effect of metformin is still controversial. AIMS: To assess the renoprotective effect of metformin in patients with type 2 diabetes. METHODS: This retrospective observational multicenter cohort study included 316,693 patients with type 2 diabetes from seven hospital. After age, gender, medical year, baseline estimated glomerular filtration rate (eGFR), urine protein (dipstick), glycated hemoglobin (HbA1C) and propensity score matching; a total of 13,096 metformin and 13,096 non-metformin patients were included. The main results were doubling of serum creatinine, eGFR ≤ 15 mL/min/1.73 m2 and end stage kidney disease (ESKD). RESULTS: After conducting a multivariable logistic regression analysis on the variables, the metformin group was revealed to have better renal outcomes than non-metformin group, including a lower incidence of doubling of serum creatinine (hazard ratio [HR], 0.71; 95% CI, 0.65-0.77), eGFR ≤ 15 mL/min/1.73 m2 (HR 0.61; 95% CI 0.53-0.71), and ESKD (HR 0.55; 95% CI 0.47-0.66). The subgroup analyses revealed a consistent renoprotective effect across patients with various renal functions. Furthermore, when considering factors such as age, sex, comorbidities, and medications in subgroup analyses, it consistently showed that the metformin group experienced a slower deterioration in renal function across nearly all patient subgroups. CONCLUSIONS: Metformin decreased the risk of renal function deterioration.

Simultaneous detection of multiple microRNAs based on fluorescence resonance energy transfer under a single excitation wavelength.

MicroRNAs (miRNAs) play a key role in physiological processes, and their dysregulation is closely related to various human diseases. Simultaneous detection of multiple miRNAs is pivotal to cancer diagnosis at an early stage. However, most multicomponent analyses generally involve multiple excitation wavelengths, which are complicated and often challenging to simultaneously acquire multiple detection signals. In this study, a convenient and sensitive sensor was developed to simultaneously detection of multiple miRNAs under a single excitation wavelength through the fluorescence resonance energy transfer between the carbon dots (CDs)/quantum dots (QDs) and graphene oxide (GO). A hybridization chain reaction (HCR) was triggered by miRNA-141 and miRNA-21, resulting in the high sensitivity with a limit of detection (LOD) of 50 pM (3σ/k) for miRNA-141 and 60 pM (3σ/k) for miRNA-21. This simultaneous assay also showed excellent specificity discrimination against the mismatch. Furthermore, our proposed method successfully detected miRNA-21 and miRNA-141 in human serum samples at a same time, indicating its diagnostic potential in a clinical setting.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

The roles of neural stem cells in myelin regeneration and repair therapy after spinal cord injury.

Spinal cord injury (SCI) is a complex tissue injury that results in a wide range of physical deficits, including permanent or progressive disabilities of sensory, motor and autonomic functions. To date, limitations in current clinical treatment options can leave SCI patients with lifelong disabilities. There is an urgent need to develop new therapies for reconstructing the damaged spinal cord neuron-glia network and restoring connectivity with the supraspinal pathways. Neural stem cells (NSCs) possess the ability to self-renew and differentiate into neurons and neuroglia, including oligodendrocytes, which are cells responsible for the formation and maintenance of the myelin sheath and the regeneration of demyelinated axons. For these properties, NSCs are considered to be a promising cell source for rebuilding damaged neural circuits and promoting myelin regeneration. Over the past decade, transplantation of NSCs has been extensively tested in a variety of preclinical models of SCI. This review aims to highlight the pathophysiology of SCI and promote the understanding of the role of NSCs in SCI repair therapy and the current advances in pathological mechanism, pre-clinical studies, as well as clinical trials of SCI via NSC transplantation therapeutic strategy. Understanding and mastering these frontier updates will pave the way for establishing novel therapeutic strategies to improve the quality of recovery from SCI.

Quantifying and Modeling the Crystallinity of Polymers Confined in Nanopores.

We propose a methodology to characterize the crystalline content of interfacial polymer layers in systems confined at the nanoscale level in a 2D geometry. Based on the crystallinity data of a set of polymers, we introduce a simple model to describe the gradient in crystallinity introduced by confining polymer chains in nanopores. Our model underscores the pivotal role that interfaces play in crystallization and unequivocally contradicts the existence of interfacial "dead" layers where crystallization cannot take place. Further, we verified that the organization of crystals near the pore walls resembles the macromolecular architecture of adsorbed layers, hinting at a strong interplay between crystallization and adsorption.

Study on the failure mechanism of high-temperature granite under two cooling modes.

In the geothermal development of hot dry rock (HDR), both the drilling of the wellbore and the heat exchange of the heat reservoir involve the effects of different cold and hot conditions on the high-temperature rock mass. The testing machine for rock mechanics was used to conduct a uniaxial compression test and carry out micro testing on the treated samples; furthermore, with the help of scanning electron microscopy the fracture mechanism of granite subjected to different temperatures and cooling methods was studied. The results show: (1) With the gradual increase in temperature, the compressive strength of granite under the two cooling methods gradually decreases. (2) The failure modes of the samples under the two cooling methods are mainly shear failure of the "Y" type. The degree of damage of the sample under water cooling is significantly greater than that under natural cooling. Electron micrographs could confirm these results. (3) It can be obtained by testing the mineral composition and element changes of granite at different temperatures. When the temperature reaches 600℃, its change is more pronounced. The results of this study can provide a theoretical reference for the failure of the wellbore and the degree of fracture of the thermal reservoir rock mass during geothermal development.

The relationship between cell density and cell count differs among Saccharomyces yeast species.

There is a recent push to develop wild and non-domesticated Saccharomyces yeast strains into useful model systems for research in ecology and evolution. Yet, the variation between species and strains in important population parameters remains largely undescribed. Here, we investigated the relationship between two commonly used measures in microbiology to estimate growth rate - cell density and cell count - in 23 strains across all eight Saccharomyces species . We found that the slope of this relationship significantly differs among species and a given optical density (OD) does not translate into the same number of cells across species. We provide a cell number calculator based on our OD measurements for each strain used in this study. Surprisingly, we found a slightly positive relationship between cell size and the slope of the cell density-cell count relationship. Our results show that the strain- and species-specificity of the cell density and cell count relationship should be taken into account, for instance when running competition experiments requiring equal starting population sizes or when estimating the fitness of strains with different genetic backgrounds in experimental evolution studies.

CCDC50 mediates the clearance of protein aggregates to prevent cellular proteotoxicity.

Protein aggregation caused by the disruption of proteostasis will lead to cellular cytotoxicity and even cell death, which is implicated in multiple neurodegenerative diseases. The elimination of aggregated proteins is mediated by selective macroautophagy receptors, which is termed aggrephagy. However, the identity and redundancy of aggrephagy receptors in recognizing substrates remain largely unexplored. Here, we find that CCDC50, a highly expressed autophagy receptor in brain, is recruited to proteotoxic stresses-induced polyubiquitinated protein aggregates and ectopically expressed aggregation-prone proteins. CCDC50 recognizes and further clears these cytotoxic aggregates through autophagy. The ectopic expression of CCDC50 increases the tolerance to stress-induced proteotoxicity and hence improved cell survival in neuron cells, whereas CCDC50 deficiency caused accumulation of lipid deposits and polyubiquitinated protein conjugates in the brain of one-year-old mice. Our study illustrates how aggrephagy receptor CCDC50 combats proteotoxic stress for the benefit of neuronal cell survival, thus suggesting a protective role in neurotoxic proteinopathy.

Alternative dimethylsulfoniopropionate biosynthesis enzymes in diverse and abundant microorganisms.

Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.