Artificial Intelligence Assessment of Biological Age from Transthoracic Echocardiography: Discrepancies to Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated by artificial intelligence based on various sources. OBJECTIVES: We aimed to test whether convolutional neural networks could be trained to estimate the age and predict the sex using standard transthoracic echocardiography (TTE), and to evaluate its prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (N=556). Finally, a prospective cohort of handheld point-of-care ultrasound (POCUS) devices (N=319; ClinicalTrials.Gov NCT05455541) was used to confirm the findings. Multivariate Cox regression model was used to investigate the association between age-estimation and chronological age with overall survival. RESULTS: The mean average error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve (AUC) of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥ 5 years of chronological age was associated with an independent 34% increased risk of death during follow-up (p<0.001). CONCLUSIONS: Applying artificial intelligence to the standard TTE allows prediction of sex and estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

Activation of ASIC3/ERK pathway by paeoniflorin improves intestinal fluid metabolism and visceral sensitivity in slow transit constipated rats.

Slow transit constipation (STC) is one of the most common gastrointestinal disorders in children and adults worldwide. Paeoniflorin (PF), a monoterpene glycoside compound extracted from the dried root of Paeonia lactiflora, has been found to alleviate STC, but the mechanisms of its effect remain unclear. The present study aimed to investigate the effects and mechanisms of PF on intestinal fluid metabolism and visceral sensitization in rats with compound diphenoxylate-induced STC. Based on the evaluation of the laxative effect, the abdominal withdrawal reflex test, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry were used to detect the visceral sensitivity, fluid metabolism-related proteins, and acid-sensitive ion channel 3/extracellular signal-regulated kinase (ASIC3/ERK) pathway-related molecules. PF treatment not only attenuated compound diphenoxylate-induced constipation symptoms and colonic pathological damage in rats but also ameliorated colonic fluid metabolic disorders and visceral sensitization abnormalities, as manifested by increased colonic goblet cell counts and mucin2 protein expression, decreased aquaporin3 protein expression, improved abdominal withdrawal reflex scores, reduced visceral pain threshold, upregulated serum 5-hydroxytryptamine, and downregulated vasoactive intestinal peptide levels. Furthermore, PF activated the colonic ASIC3/ERK pathway in STC rats, and ASIC3 inhibition partially counteracted PF's modulatory effects on intestinal fluid and visceral sensation. In conclusion, PF alleviated impaired intestinal fluid metabolism and abnormal visceral sensitization in STC rats and thus relieved their symptoms through activation of the ASIC3/ERK pathway.

Research advances in the influence of lipid metabolism on cognitive impairment.

Cognitive impairment (CI) is a mental disorder related to cognition and understanding, which is mainly categorized into mild CI and senile dementia. This disease is associated with multiple factors, such as chronic brain injury, aging, chronic systemic disease, mental state, and psychological factors. However, the pathological mechanism of CI remains unclear; it is usually associated with such underlying diseases as diabetes and hyperlipidemia. It has been demonstrated that abundant lipid metabolism indexes in the human body are closely related to CI, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein, and so forth. As a crucial risk factor for CI, hyperlipidemia is of great significance in the occurrence and development of CI. However, the specific correlation between dyslipidemia and CI is still not fully elucidated. Besides, the efficacy of lipid-lowering drugs in the prophylaxis and treatment of CI has not been clarified. In this study, relevant advances in the influence of lipid metabolism disorders in CI will be reviewed, in an attempt to explore the effect of mediating blood lipid levels on the prophylaxis and treatment of CI, thus providing a reference for its clinical management.

Is RNA editing truly absent in the complex thalloid liverworts (Marchantiopsida)? Evidence of extensive RNA editing from Cyathodium cavernarum.

RNA editing is a crucial modification in plants' organellar transcripts that converts cytidine to uridine (C-to-U; and sometimes uridine to cytidine) in RNA molecules. This post-transcriptional process is controlled by the PLS-class protein with a DYW domain, which belongs to the pentatricopeptide repeat (PPR) protein family. RNA editing is widespread in land plants; however, complex thalloid liverworts (Marchantiopsida) are the only group reported to lack both RNA editing and DYW-PPR protein. The liverwort Cyathodium cavernarum (Marchantiopsida, Cyathodiaceae), typically found in cave habitats, was newly found to have 129 C-to-U RNA editing sites in its chloroplast and 172 sites in its mitochondria. The Cyathodium genus, specifically C. cavernarum, has a large number of PPR editing factor genes, including 251 DYW-type PPR proteins. These DYW-type PPR proteins may be responsible for C-to-U RNA editing in C. cavernarum. Cyathodium cavernarum possesses both PPR DYW proteins and RNA editing. Our analysis suggests that the remarkable RNA editing capability of C. cavernarum may have been acquired alongside the emergence of DYW-type PPR editing factors. These findings provide insight into the evolutionary pattern of RNA editing in land plants.

Modeling competitive biosorption for methylene blue removal on rape straw powders using response surface methodology in a ternary dye aqueous solution.

The improvement of biosorption efficiency for selective dye removal in a multi-dye aqueous system has become an increasingly significant research topic. However, the competitive effects of coexisting dyes and the target dye in such systems remain uncertain due to complex interactions between adsorbent and coexisting dyes. Therefore, in this research, response surface methodology (RSM) model was effectively employed to investigate the competitive effects of allura red (AR) and malachite green (MG) on methylene blue (MB) removal in a ternary dye aqueous system using three different parts of rape straw powders. In the current design of RSM, the initial concentrations of AR and MG dyes ranging from 0 mg·L-1 to 500 mg·L-1 were considered as influencing factors, while the removal rates of MB on adsorbents at an initial concentration of 500 mg·L-1 were established as response values. The RSM models exhibited high correlation coefficients with adjusted R2 values of 0.9908 (pith core), 0.9870 (seedpods), and 0.9902 (shells), respectively, indicating a close fitted between predicted and actual values. The proposed models indicated that the perturbation effects of initial AR and MG concentrations were observed on the removal rates of MB by three types of rape straw powders in a ternary dye aqueous system, resulting in a decrease in MB removal rates, particularly at higher initial AR concentration due to stronger competitive effects compared to initial MG concentration. The structures of rape straw powders, including pith core, seedpods and shell, were analyzed using scanning eletron microscoe (SEM), energy dispersive spectroscopy (EDS), N2 physisorption isotherm, frourier transform infared spectroscopy (FTIR), Zeta potential classes and fluorescence spectrum before and after adsorption of MB in various dye aqueous systems. The characteristics of rape straw powders suggested that similar adsorption mechanisms, such as electrostatic attraction, pore diffusion, and group complex formation for MB, AR, and MG, respectively, occurred on the surfaces of adsorbents during their respective adsorption processes. This leads to significant competitive effects on the removal rates of MB in a ternary dye aqueous system, which are particularly influenced by initial AR concentrations as confirmed through fluorescence spectrum analysis.

Impact of AR and MG on MB removal was analyzed using simple methodologies.Competitive behaviors between AR, MG and MB were understood through RSM.Intense restrain effects on MB removal were revealed by AR concentration.

CircSCUBE3 promoted ferroptosis to inhibit lung adenocarcinoma progression.

CircRNAs can regulate ferroptosis and affect cancer development and are promising biomarkers and therapeutic targets in lung cancer. circSCUBE3 is expressed in lung adenocarcinoma (LUAD) tissues. In this study, our purpose was to study the role and regulatory mechanism of circSCUBE3 in LUAD ferroptosis. circSCUBE3 was identified to be significantly downregulated in LUAD samples and cell lines. The expression of biomarkers related to lipid oxidation (4-HNE) and ferroptosis (Ptgs2) was both downregulated in LUAD tissues, suggesting the ferroptosis resistance in LUAD. Erastin, a ferroptosis inducer, was used to stimulate the LUAD cells for 48 h. The cell viability, 4-HNE and Ptgs2 level of LUAD cells were decreased by exposure to erastin while the expression of circSCUBE3 was not significantly altered. We then overexpressed circSCUBE3 in LUAD cells and found it decreased the GSH level and GSH/GSSG ratio in LUAD cells. CircSCUBE3 might serve as an independent factor of ferroptosis and may induce ferroptosis in LUAD by inhibiting GSH synthesis. The loss-of-function experiments were conducted, and circSCUBE3 deficiency reversed the erastin-induced reduction in cell viability, GSH level, GSH/GSSG ratio, mitochondrial membrane potential and elevation in MDA content, Ptgs2, 4-HNE expression as well as lipid ROS production. CircSCUBE3 negatively regulated GPX4 expression in LUAD cells, and the silencing of GPX4 counteracted the impact of circSCUBE3 deficiency on LUAD cell viability as well as ferroptosis, suggesting that circSCUBE3 regulated the GPX4-mediated GSH synthesis in LUAD. CircSCUBE3 was to bind to CREB, which activated the transcription of GPX4. CircSCUBE3 negatively regulated GPX4 expression by competitively interacting with CREB. In the tumor-bearing mouse models, circSCUBE3 silencing promoted tumor growth and reversed the erastin treatment-induced inhibition on tumorigenesis in vivo. In conclusion, circSCUBE3 inhibited LUAD development by promoting ferroptosis via the CREB/GPX4/GSH axis, which might provide a novel option for the LUAD targeted therapy.

Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship.

Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.

Cediranib enhances the transcription of MHC-I by upregulating IRF-1.

Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8+ T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy.

Circulating biomarkers in the diagnosis and prognosis of immune checkpoint inhibitor-related myocarditis: time for a risk-based approach.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoints and therefore activate immune cells, allowing them to recognize and attack cancer cells. ICIs have revolutionized oncology practice, but their use has been complicated by immune-related adverse events (irAEs). Of cardiovascular (CV) irAEs, ICI-related myocarditis has received significant attention due to high mortality rates, ranging from 25% to 50%, despite its overall low incidence. Establishing the early diagnosis of ICI-myocarditis is important for early initiation of steroids and consideration of hospitalization in patients who are at risk for hemodynamic compromise and need high acuity care in a tertiary setting. In this review, we summarize the diagnostic and prognostic tools for ICI-myocarditis, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, with emphasis on circulating biomarkers. Cardiac troponins (cTns) are an essential component of the diagnosis of ICI-myocarditis, and we provide a summary of the recent studies that utilized different assays (cTnI vs. cTnT) and outcomes (diagnosis vs. prognosis including major adverse cardiac outcomes). With the exponential increase in ICI use across different oncology indications, there is a major need to include biomarkers in risk stratification to guide diagnosis and treatment. Our review proposes a framework for future multisite registries, including cTn evaluation at baseline and at the time of irAE suspicion, with development of central biobanking to allow head-to-head evaluation and clinical validation of different biomarker assays in ICI-myocarditis. This approach, with the inclusion of CV biomarkers into clinical and pragmatic oncology trials, holds promise to improve the early recognition and management of ICI-myocarditis and CV irAEs, thus leading to better outcomes.

Pulmonary vascular dysfunction without pulmonary hypertension: A distinct phenotype in idiopathic pulmonary fibrosis.

Pulmonary vascular dysfunction in the absence of pulmonary hypertension (PH) has been observed in patients with idiopathic pulmonary fibrosis (IPF). We describe the prevalence and etiology of elevated pulmonary vascular resistance (PVR) without PH among patients with IPF. Hemodynamic, echocardiographic, and functional respiratory imaging (FRI) data was compared between patients with IPF without PH with normal (<3 wood units) and elevated PVR (≥3 wood units). Mortality between these two groups were compared to patients with IPF and PH. Of 205 patients with IPF, there were 146 patients without PH, of whom 114 (78.1%) had a normal PVR and 32 (21.9%) who had a high PVR. Functional testing and hemodynamics were similar in the two groups, except for the cardiac index which was significantly lower in patients with a high PVR (2.3 vs. 2.6 L/min/m2; p = 0.004). Echocardiographic comparison demonstrated a higher tricuspid regurgitant velocity in those with a high PVR (3.4 vs 3.0 m/s; p = 0.046). FRI revealed proportionately fewer large vessels as a proportion of the vasculature in the patients without PH and elevated PVRs. Among patients without PH, PVR was associated with increased mortality. In conclusion, patients with IPF without PH but a high PVR appear to be a distinct phenotype with a prognosis between those with and without PH, likely reflecting the continuum of vascular dysfunction. The basis for this unique hemodynamic profile could not be definitively discerned although FRI suggested an aberrant anatomical vascular response.

Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy.

Hepatitis B virus (HBV) chronically infects 296 million people worldwide and causes more than 820,000 deaths annually due to cirrhosis and hepatocellular carcinoma. Current standard-of-care medications for chronic hepatitis B (CHB) include nucleos(t)ide analogue (NA) viral DNA polymerase inhibitors and pegylated interferon alpha (PEG-IFN-α). NAs can efficiently suppress viral replication and improve liver pathology, but not eliminate or inactivate HBV covalently closed circular DNA (cccDNA). CCC DNA is the most stable HBV replication intermediate that exists as a minichromosome in the nucleus of infected hepatocyte to transcribe viral RNA and support viral protein translation and genome replication. Consequentially, a finite duration of NA therapy rarely achieves a sustained off-treatment suppression of viral replication and life-long NA treatment is most likely required. On the contrary, PEG-IFN-α has the benefit of finite treatment duration and achieves HBsAg seroclearance, the indication of durable immune control of HBV replication and functional cure of CHB, in approximately 5% of treated patients. However, the low antiviral efficacy and poor tolerability limit its use. Understanding how IFN-α suppresses HBV replication and regulates antiviral immune responses will help rational optimization of IFN therapy and development of novel immune modulators to improve the rate of functional cure. This review article highlights mechanistic insight on IFN control of HBV infection and recent progress in development of novel IFN regimens, small molecule IFN mimetics and combination therapy of PEG-IFN-α with new direct-acting antivirals and therapeutic vaccines to facilitate the functional cure of CHB.

To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis.

Neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and motor neuron disease, are diseases characterized by neuronal damage and dysfunction. NDs are considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) and complex pathophysiological processes. Previous studies have found that neuroinflammation and typical microglial activation are important mechanisms of NDs, leading to neurological dysfunction and disease progression. Pyroptosis is a new mode involved in this process. As a form of programmed cell death, pyroptosis is characterized by the expansion of cells until the cell membrane bursts, resulting in the release of cell contents that activates a strong inflammatory response that promotes NDs by accelerating neuronal dysfunction and abnormal microglial activation. In this case, abnormally activated microglia release various pro-inflammatory factors, leading to the occurrence of neuroinflammation and exacerbating both microglial and neuronal pyroptosis, thus forming a vicious cycle. The recognition of the association between pyroptosis and microglia activation, as well as neuroinflammation, is of significant importance in understanding the pathogenesis of NDs and providing new targets and strategies for their prevention and treatment.

Thrifty effect of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic effectiveness: A prospective, triple-blind, randomized controlled, polycentric clinical trial.

Aim: To investigate the thrifty effects of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic efficacy. Methods: Four-hundred and twenty patients were divided into the control group (CON group), the S-ketamine 0.2 mg/kg group (ES0.2 group), and the S-ketamine 0.3 mg/kg group (ES0.3 group) randomly. Major indicators include the Visual Analogue Scale (VAS), the times of compression with analgesic pumps after surgery, and analgesic drug consumption from anesthesia induction to 48 h after surgery. Minor records include vital signs, the use of vasoactive drugs, the Ramsay scores, the occurrence of adverse events including nervous system reaction, and the patient's satisfaction with anesthesia. Results: Compared with the CON group, VAS scores decreased in the ES0.2 and ES0.3 groups (p < 0.05). At 10 min after extubation, the VAS scores of the ES0.3 group were lower than that of the ES0.2 group (p < 0.05). The total number of compression with analgesic pumps of the ES0.3 group was lower than that of the CON group (p < 0.05). The opioid consumption after surgery of the ES0.3 group was lower than those of the CON group and the ES0.2 group (p < 0.05). The ES0.3 group's heart rate (HR) was faster but the use of vasoactive, drug consumption was less than the other two groups (p < 0.05). There were no significant differences in the incidence of postoperative adverse events and anesthetic satisfaction among the three groups. Conclusion: Subanesthetic-dose S-ketamine at 0.2-0.3 mg/kg especially the 0.3 mg/kg in general anesthesia induction can safely and effectively reduce postoperative pain and save postoperative opioid consumption.

The effective doses of remimazolam besylate in the procedural sedation of endoscopic retrograde cholangiopancreatography.

This study aimed to determine the values of the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate used in the procedural sedation of endoscopic retrograde cholangiopancreatography (ERCP). Sixty patients who fulfilled the inclusion and exclusion criteria of this study were selected. Sufentanil was administered intravenously and remimazolam besylate was administered 2 min later. ERCP treatment was feasible when the modified alertness/sedation (MOAA/S) score was ≤2. If choking or movement occurred during duodenoscope placement, it was considered as a positive reaction. The dose was increased in the next patient; otherwise, it was considered as a negative reaction, and the dose was reduced in the next patient. The ED50 and ED95 values and 95% confidence interval (CI) of remimazolam besylate were calculated by Probit regression analysis. All 60 patients completed the trial. The ED50 and ED95 values of remimazolam besylate were 0.196 and 0.239 mg/kg, respectively, for the procedural sedation of ERCP. The time of MOAA/S score ≤ 2 was (82.58 ± 21.70) s, and the mean time of awakening was (9.03 ± 5.64) min. Transient hypotension was observed in two patients without medical intervention. The ED50 and ED95 values of remimazolam besylate used in the procedural sedation of ERCP were 0.196 and 0.239 mg/kg, and the dose of the medications has definite efficacy and good safety.

Causal relationship between Alzheimer's disease and cardiovascular disease: a bidirectional Mendelian randomization analysis.

Observational studies suggest that cardiovascular disease (CVD) increases the risk of developing Alzheimer's disease (AD). However, the causal relationship between the two is not clear. This study applied a two-sample bidirectional Mendelian randomization method to explore the causal relationship between CVD and AD. Genome-wide association study (GWAS) data from 46 datasets of European populations (21,982 cases of AD and 41,944 controls) were utilized to obtain genetic instrumental variables for AD. In addition, genetic instrumental variables for atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), coronary heart disease (CHD), angina pectoris (AP), and ischemic stroke (IS) (including large-artery atherosclerotic stroke [LAS] and cardioembolic stroke [CES]) were selected from GWAS data of European populations (P < 5E-8). The inverse variance weighting method was employed as the major Mendelian randomization analysis method. Genetically predicted AD odds ratios (OR) (1.06) (95% CI: 1.02-1.10, P = 0.003) were linked to higher AP analysis. A higher genetically predicted OR for CES (0.9) (95% CI 0.82-0.99, P = 0.02) was linked to a decreased AD risk. This Mendelian randomized study identified AD as a risk factor for AP. In addition, CES was related to a reduced incidence of AD. Therefore, these modifiable risk factors are crucial targets for preventing and treating AD.

Revealing Inter-regional Environmental Inequities Hidden in China's Energy Transition.

Energy transition is an important way to control air pollution, but it may conflict with the economic goal of alleviating regional inequality due to its inherently different cost burdens. As one of the effective measures of energy transition, this paper takes small coal-fired boiler (SCB) upgrading as an example to explore the regional mismatch between upgrading costs and health benefits. Here, we construct a boiler-level inventory of SCB upgrades for the North China Plain (NCP) during 2013-2017 and propose an integrated modeling framework to quantify the spatial contribution of economic costs and health benefits associated with SCB upgrading. We find that although the total health benefits could offset the total costs for the entire region, the developed municipalities (Beijing and Tianjin) are likely to gain more health benefits from less-developed neighboring provinces at lower costs. These developed municipalities contribute only 14% to the total health benefits but gain 21% of the benefits within their territories, 56% of which come from neighboring provinces. Their benefits are approximately 5.6 times their costs, which is much higher than the 1.5 benefit-cost ratio in neighboring provinces. Our findings may be useful in shaping more equitable and sound environmental policies in China or other regions of the world with serious coal-related air pollution.

The plant-unique protein DRIF1 coordinates with sorting nexin 1 to regulate membrane protein homeostasis.

Membrane protein homeostasis is fine-tuned by the cellular pathways for vacuolar degradation and recycling, which ultimately facilitate plant growth and cell-environment interactions. The endosomal sorting complex required for transport (ESCRT) machinery plays important roles in regulating intraluminal vesicle (ILV) formation and membrane protein sorting to vacuoles. We previously showed that the plant-specific ESCRT component FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING1 (FREE1) performs multiple functions in plants, although the underlying mechanisms remain elusive. In this study, we performed a suppressor screen of the FREE1-RNAi mutant and identified and characterized 2 suppressor of free1 (sof) mutants in Arabidopsis (Arabidopsis thaliana). These mutants, sof10 and sof641, result in a premature stop codon or a missense mutation in AT5G10370, respectively. This gene was named DEAH and RING domain-containing protein as FREE1 suppressor 1 (DRIF1). DRIF1 has a homologous gene, DRIF2, in the Arabidopsis genome with 95% identity to DRIF1. The embryos of drif1 drif2 mutants arrested at the globular stage and formed enlarged multivesicular bodies (MVBs) with an increased number of ILVs. DRIF1 is a membrane-associated protein that coordinates with retromer component sorting nexin 1 to regulate PIN-FORMED2 recycling to the plasma membrane. Altogether, our data demonstrate that DRIF1 is a unique retromer interactor that orchestrates FREE1-mediated ILV formation of MVBs and vacuolar sorting of membrane proteins for degradation in plants.

Seasonal variation in soil algal community structure in different forest plantations in subtropic China.

Algae exert great impact on soil formation and biogeochemical cycling. However, there is no full understanding of the response of soil algal community structure to the seasonal fluctuations in temperature and moisture and changes of soil physicochemical properties across different forests. Here, based on 23S rRNA gene sequencing, we analyzed soil algal community structure in four different forest plantations in two seasons and examined soil physiochemical properties. The results showed the significantly seasonal variation in soil algal community structure, with the higher overall diversity in summer than in winter. In addition, there existed significant correlations between soil algae (species composition, relative abundance, diversity index) and physicochemical properties (pH, total phosphorus, organic matter and nitrate nitrogen), suggesting that edaphic characteristics are also largely responsible for the variation in soil algal community. Nevertheless, the seasonal variation in algal community structure was greater than the variation across different forest plantations. This suggest temperature and moisture are more important than soil physicochemical properties in determining soil algal community structure. The findings of the present study enhance our understanding of the algal communities in forest ecosystems and are of great significance for the management and protection of algal ecosystem.

Recent advances in plant endomembrane research and new microscopical techniques.

The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes, and the lysosome/vacuole. Membrane trafficking between distinct compartments is mainly achieved by vesicular transport. As the endomembrane compartments and the machineries regulating the membrane trafficking are largely conserved across all eukaryotes, our current knowledge on organelle biogenesis and endomembrane trafficking in plants has mainly been shaped by corresponding studies in mammals and yeast. However, unique perspectives have emerged from plant cell biology research through the characterization of plant-specific regulators as well as the development and application of the state-of-the-art microscopical techniques. In this review, we summarize our current knowledge on the plant endomembrane system, with a focus on several distinct pathways: ER-to-Golgi transport, protein sorting at the TGN, endosomal sorting on multivesicular bodies, vacuolar trafficking/vacuole biogenesis, and the autophagy pathway. We also give an update on advanced imaging techniques for the plant cell biology research.

Anti-inflammatory effect of two novel peptides derived from Binglangjiang buffalo whey protein in lipopolysaccharide-stimulated RAW264.7 macrophages.

Whey protein hydrolysate from Binglangjiang buffalo, a unique genetic resource, has anti-inflammatory activity, but its anti-inflammatory composition and effects are unknown. The aim of this study was to investigate the anti-inflammatory peptides from Binglangjiang buffalo whey protein hydrolysate. A total of 1483 peptides were identified using LC-MS/MS, and 12 peptides were chosen for chemical synthesis using peptidomics, and then two novel anti-inflammatory peptides (DQPFFHYN (DN8) and YSPFSSFPR (YR9)) were screened out using LPS-stimulated RAW264.7 cells. The molecular weights of DN8 and YR9 with ß-turn conformations were 1067.458 Da and 1087.52 Da, respectively, and showed a high in-vitro safety profile and thermal stability, but were intolerant to pepsin. Furthermore, ELISA and Western blot analysis indicated that peptides DN8 and YR9 significantly suppressed the secretion of pro-inflammatory cytokines NO, TNF-α, and IL-6 and the expression of mediators iNOS, TNF-α, and IL-6 in LPS-stimulated RAW264.7 cells. The study provides insights into the development of novel food-based anti-inflammatory nutritional supplements.