Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

Association between synoptic types in Beijing and acute myocardial infarction hospitalizations: A comprehensive analysis of environmental factors.

BACKGROUND: Environmental factors like air pollution and temperature can trigger acute myocardial infarction (AMI). However, the link between large-scale weather patterns (synoptic types) and AMI admissions has not been extensively studied. This research aimed to identify the different synoptic air types in Beijing and investigate their association with AMI occurrences. METHODS: We analyzed data from Beijing between 2013 and 2019, encompassing 2556 days and 149,632 AMI cases. Using principal component analysis and hierarchical clustering, classification into distinct synoptic types was conducted based on weather and pollution measurements. To assess the impact of each type on AMI risk over 14 days, we employed a distributed lag non-linear model (DLNM), with the reference being the lowest risk type (Type 2). RESULTS: Four synoptic types were identified: Type 1 with warm, humid weather; Type 2 with warm temperatures, low humidity, and long sunshine duration; Type 3 with cold weather and heavy air pollution; and Type 4 with cold temperatures, dryness, and high wind speed. Type 4 exhibited the greatest cumulative relative risk (CRR) of 1.241 (95%CI: 1.150, 1.339) over 14 days. Significant effects of Types 1, 3, and 4 on AMI events were observed at varying lags: 4-12 days for Type 1, 1-6 days for Type 3, and 1-11 days for Type 4. Females were more susceptible to Types 1 and 3, while individuals younger than 65 years old showed increased vulnerability to Types 3 and 4. CONCLUSION: Among the four synoptic types identified in Beijing from 2013 to 2019, Type 4 (cold, dry, and windy) presented the highest risk for AMI hospitalizations. This risk was particularly pronounced for males and people under 65. Our findings collectively highlight the need for improved methods to identify synoptic types. Additionally, developing a warning system based on these synoptic conditions could be crucial for prevention.

Risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly patients infected with the Omicron variant of SARS-CoV-2: a retrospective study at Shanghai Fourth People's Hospital, School of Medicine, Tongji University.

Introduction: In elderly patients infected with the Omicron variant, disease progression to severe infection can result in poor outcomes. This study aimed to identify risk and protective factors associated with disease progression to severe infection and viral clearance time in elderly Omicron-infected patients. Methods: Shanghai Fourth People's Hospital, School of Medicine, Tongji University, was officially designated to provide treatment to patients with COVID-19. This study was conducted on confirmed Omicron cases admitted to the hospital between 10 April 2022 and 21 June 2022. In total, 1,568 patients aged 65 years or older were included. We conducted a retrospective, observational study using logistic regression to analyze risk and protective factors for the development of severe disease and Cox proportional hazards regression models to analyze factors influencing viral clearance time. Results: Aged over 80 years, having 2 or more comorbidities, combined cerebrovascular disease, chronic neurological disease, and mental disorders were associated with the development of severe disease, and full vaccination was a protective factor. Furthermore, aged over 80 years, combined chronic respiratory disease, chronic renal disease, cerebrovascular disease, mental disorders, and high viral load were associated with prolonged viral clearance time, and full vaccination was a protective factor. Discussion: This study analyzed risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly Omicron-infected patients. Aged patients with comorbidities had a higher risk of developing severe infection and had longer viral clearance, while vaccination protected them against the Omicron infection.

Protective effects of oyster polypeptide on cyclophosphamide-induced immunosuppressed rats.

BACKGROUND: Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H-NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. RESULTS: Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide-induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin­6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. CONCLUSION: This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide-induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry.

Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice.

The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. In this study, a wild bird-origin H6N2 AIV was isolated from the East Asian-Australasian migratory flyway region located in Liaoning Province. This H6N2 virus initially expressed limited replication in mice. However, after one passage in mice, the virus acquired two mutations, PB2 E627K and HA A110V. The mutant displayed enhanced replication both in vitro and in vivo, proving lethal to mice. But the mutant retained the α-2, 3-linked sialic acid binding property and failed to transmit in guinea pigs. We explored the molecular mechanisms underlying the pathogenicity difference between the wild type and the mutant. Our findings revealed that PB2 E627K dramatically enhanced the polymerase activity of the H6N2 virus, while the HA A110V mutation decreased the pH of HA activation. This study demonstrated that the H6N2 subtype wild bird-origin AIV easily acquired the mammalian adaptation. The monitoring and evaluation of H6 wild bird-origin AIV should be strengthened.

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases.

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain-gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA- and DR-related drugs for digestive system diseases.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

OsNAC120 balances plant growth and drought tolerance by integrating GA and ABA signaling in rice.

The crosstalk between gibberellin (GA) and abscisic acid (ABA) signaling is crucial for balancing plant growth and adaption to environmental stress. Nevertheless, the molecular mechanism of their mutual antagonism still remains to be fully clarified. In this study, we found that knockout of the rice NAC (NAM, ATAF1/2, CUC2) transcription factor gene OsNAC120 inhibits plant growth but enhances drought tolerance, whereas OsNAC120 overexpression produces the opposite results. Exogenous GA can rescue the semi-dwarf phenotype of osnac120 mutants, and further study showed that OsNAC120 promotes GA biosynthesis by transcriptionally activating the GA biosynthetic genes OsGA20ox1 and OsGA20ox3. The DELLA protein SLENDER RICE1 (SLR1) interacts with OsNAC120 and impedes its transactivation ability, and GA treatment can remove the inhibition of transactivation activity caused by SLR1. On the other hand, OsNAC120 negatively regulates rice drought tolerance by repressing ABA-induced stomatal closure. Mechanistic investigation revealed that OsNAC120 inhibits ABA biosynthesis via transcriptional repression of the ABA biosynthetic genes OsNCED3 and OsNCED4. Rice OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (OsSAPK9) physically interacts with OsNAC120 and mediates its phosphorylation, which results in OsNAC120 degradation. ABA treatment accelerates OsNAC120 degradation and reduces its transactivation activity. Together, our findings provide evidence that OsNAC120 plays critical roles in balancing GA-mediated growth and ABA-induced drought tolerance in rice. This research will help us to understand the mechanisms underlying the trade-off between plant growth and stress tolerance and to engineer stress-resistant, high-yielding crops.

Geochemical Analysis of Dolomite in the Fourth Member of the Upper Sinian Dengying Formation, Northern Sichuan Basin, China.

The fourth member of the Sinian Dengying Formation in northern Sichuan was reformed by multistage diagenetic fluids. It is beneficial to systematically analyze the diagenetic evolution of the area to clarify the sedimentary evolution of the dolomite in the fourth member of the Dengying Formation and the fluid characteristics at different diagenetic stages. In this study, the petrological characteristics, vertical sedimentary evolution, diagenetic fluid stages, and diagenetic environment of Dengsi dolomite were analyzed by using carbon-oxygen strontium isotopes, rare-earth elements, major and trace elements, combined with the supporting thin section identification and cathodoluminescence techniques, and the source and properties of diagenetic fluid of Dengsi dolomite in different diagenetic environments were determined. The results show that (1) during the deposition period of the fourth member of the Dengying Formation, the water body showed a trend from shallow to deep and then steadily to shallow, which was in a shallow freshwater reducing environment and had a warm and humid paleoclimate environment; (2) the dolomite of the fourth member of Dengying Formation in northern Sichuan is less affected by terrigenous materials. The C and O isotopes of dolomite are generally negative at the top of the fourth member of the Dengying Formation, and the top of the formation is obviously transformed into rock by atmospheric fresh water; rare-earth elements show that dolomitized fluid is dominated by primitive seawater, and the marine fluid from or flowing through the carbonaceous shale formation rich in feldspar minerals in the Qiongzhusi formation during burial period makes the rare earth elements show obvious positive EU anomalies. The high 87Sr/86Sr ratio of the surrounding rock and cement is caused by the 87Sr-rich marine fluid coming from the fault communication or along the unconformity zone; (3) since the deposition of the dolomite of the fourth member of Dengshan formation in northern Sichuan, it has experienced multistage diagenesis. The multistage cement and fillings in the pores have recorded at least seven stages of fluid activity history: during the quasi-contemporaneous period, fresh water was transformed to increase pores, and seawater was cemented to damage pores. During the supergene period, the pore size of atmospheric freshwater increased generally; during the middle deep burial period, the acid fluid was reformed to increase the porosity, the 87Sr-rich hydrocarbon-bearing fluid was used to fill the damaged pores, and the Eu2+-rich marine source fluid was used to fill the damaged pores. In the deep burial period, siliceous hydrothermal fluid filled the damaged hole.

Temperature fluctuation and acute myocardial infarction in Beijing: an extended analysis of temperature ranges and differences.

Purpose: Few studies examined the relationship between temperature fluctuation metrics and acute myocardial infarction (AMI) hospitalizations within a single cohort. We aimed to expand knowledge on two basic measures: temperature range and difference. Methods: We conducted a time-series analysis on the correlations between temperature range (TR), daily mean temperature differences (DTDmean), and daily mean-maximum/minimum temperature differences (TDmax/min) and AMI hospitalizations, using data between 2013 and 2016 in Beijing, China. The effects of TRn and DTDmeann over n-day intervals were compared, respectively. Subgroup analysis by age and sex was performed. Results: A total of 81,029 AMI hospitalizations were included. TR1, TDmax, and TDmin were associated with AMI in J-shaped patterns. DTDmean1 was related to AMI in a U-shaped pattern. These correlations weakened for TR and DTDmean with longer exposure intervals. Extremely low (1st percentile) and high (5°C) DTDmean1 generated cumulative relative risk (CRR) of 2.73 (95% CI: 1.56-4.79) and 2.15 (95% CI: 1.54-3.01). Extremely high TR1, TDmax, and TDmin (99th percentile) correlated with CRR of 2.00 (95% CI: 1.73-2.85), 1.71 (95% CI: 1.40-2.09), and 2.73 (95% CI: 2.04-3.66), respectively. Those aged 20-64 had higher risks with large TR1, TDmax, and TDmin, while older individuals were more affected by negative DTDmean1. DTDmean1 was associated with a higher AMI risk in females. Conclusion: Temperature fluctuations were linked to increased AMI hospitalizations, with low-temperature extremes having a more pronounced effect. Females and the older adult were more susceptible to daily mean temperature variations, while younger individuals were more affected by larger temperature ranges.

Comparative effects of two in situ hybridization methods for the pinewood nematode (Bursaphelenchus xylophilus).

The gene localization technique of Bursaphelenchus xylophilus (pinewood nematode, PWN) is used for study gene expression in PWNs. Two in situ hybridization methods, namely, whole-mount in situ hybridization and the cut-off method are used widely. To compare the effects of these two in situ hybridization methods, the present study investigated the patterns of two functional genes expression in PWNs. The Bx-vap-2 gene (GenBank accession number: OR228482), related to pathogenicity, and the fem-2 gene (GenBank accession number: OR228481), related to sex determination, were selected to map related genes in the whole-mount and amputated PWNs at different ages using these in situ hybridization methods. Based on the overall statistical comparison, we found that compared to the cut-off method, the whole-mount method exhibited higher staining rates and correct staining rates for the fem-2 gene and Bx-vap-2 gene. However, considering the correct staining aspect, the cut-off method yielded better staining effects on pinewood nematode sections than the whole-mount method, with clearer hybridization signal locations and less non-specific staining. In other words, the cut-off method demonstrated more precise gene localization. Both methods are applicable for gene localization, but considering the overall staining pattern, analysis of experimental results, and comprehensive experimental operations, we believe that the whole-mount method is more suitable for gene localization and expression analysis of development-related genes in pinewood nematodes. This is because intact pinewood nematodes are better suited for showcasing the continuous developmental process of development-related genes. On the other hand, considering the experimental time, accuracy of staining site, and the amount of non-specific staining, the cut-off method is more suitable for disease-related genes. Additionally, to achieve better performance, the cut-off method can be selectively applied to samples during the experimental process.

[Construction of a Risk Prediction Model for Lung Cancer Based on Lifestyle Behaviors in the UK Biobank Large-Scale Population Cohort].

Objective: To identify the risk factors related to lifestyle behaviors that affect the incidence of lung cancer, to build a lung cancer risk prediction model to identify, in the population, individuals who are at high risk, and to facilitate the early detection of lung cancer. Methods: The data used in the study were obtained from the UK Biobank, a database that contains information collected from 502 389 participants between March 2006 and October 2010. Based on domestic and international guidelines for lung cancer screening and high-quality research literature on lung cancer risk factors, high-risk population identification criteria were determined. Univariate Cox regression was performed to screen for risk factors of lung cancer and a multifactor lung cancer risk prediction model was constructed using Cox proportional hazards regression. Based on the comparison of Akaike information criterion and Schoenfeld residual test results, the optimal fitted model assuming proportional hazards was selected. The multiple factor Cox proportional hazards regression was performed to consider the survival time and the population was randomly divided into a training set and a validation set by a ratio of 7:3. The model was built using the training set and the performance of the model was internally validated using the validation set. The area under the receiver operating characteristic (ROC) curve ( AUC) was used to evaluate the efficacy of the model. The population was categorized into low-risk, moderate-risk, and high-risk groups based on the probability of occurrence of 0% to <25%, 25% to <75%, and 75% to 100%. The respective proportions of affected individuals in each risk group were calculated. Results: The study eventually covered 453 558 individuals, and out of the cumulative follow-up of 5 505 402 person-years, a total of 2 330 cases of lung cancer were diagnosed. Cox proportional hazards regression was performed to identify 10 independent variables as predictors of lung cancer, including age, body mass index (BMI), education, income, physical activity, smoking status, alcohol consumption frequency, fresh fruit intake, family history of cancer, and tobacco exposure, and a model was established accordingly. Internal validation results showed that 8 independent variables (all the 10 independent variables screened out except for BMI and fresh fruit intake) were significant influencing factors of lung cancer ( P<0.05). The AUC of the training set for predicting lung cancer occurrence at one year, five years, and ten years were 0.825, 0.785, and 0.777, respectively. The AUC of the validation set for predicting lung cancer occurrence at one year, five years, and ten years were 0.857, 0.782, and 0.765, respectively. 68.38% of the individuals who might develop lung cancer in the future could be identified by screening the high-risk population. Conclusion: We established, in this study, a model for predicting lung cancer risks associated with lifestyle behaviors of a large population. Showing good performance in discriminatory ability, the model can be used as a tool for developing standardized screening strategies for lung cancer.

Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC. Methods: Bulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multi-faceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value. Results: KIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8+ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A "writer" and "reader" genes, and negatively related to "eraser" genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil. Conclusion: KIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy.

Phytochemical constituents from rhizomes of Dryopteris crassirhizoma and their anti-inflammatory activity.

The phytochemical investigation on the rhizomes of Dryopteris crassirhizoma (Dryopteridaceae) resulted in the discovery of one novel compound, drycrassirhizomamide A (1), and one new natural product, drycrassirhizomamide B (2), as well as four known isolates, (S)-(-)-N-benzoylphenylalaninol (3), blumenol A (4), 8-C-glucosylnoreugenin (5), and dryopteroside (6). Their chemical structures were identified by NMR and mass spectroscopy. Compounds 1-2 were determined to be 1,19-diethyl 10-oxo-2,9,11,18-tetraazanonadecanedioate and C,C'-diethyl N,N'-1,6-hexanediylbis[carbamate]. The anti-inflammatory activities of these compounds were evaluated with LPS-stimulated RAW264.7 macrophage and BV2 microglia. The results showed that compounds 1-3 and 6 have inhibitory effects of NO production with IC50 values of 13.41, 30.36, 25.51, and 11.35 µM in LPS-stimulated RAW264.7 cells. Also, compounds 1 and 4-6 have abilities to inhibit NO production with the IC50 values of 40.11, 30.94, 15.76, and 16.79 µM in BV2 cells, which demonstrated that they may possess the potential anti-inflammatory activity.

Ion channels and transporters regulate nutrient absorption in health and disease.

Ion channels and transporters are ubiquitously expressed on cell membrane, which involve in a plethora of physiological process such as contraction, neurotransmission, secretion and so on. Ion channels and transporters is of great importance to maintaining membrane potential homeostasis, which is essential to absorption of nutrients in gastrointestinal tract. Most of nutrients are electrogenic and require ion channels and transporters to absorb. This review summarizes the latest research on the role of ion channels and transporters in regulating nutrient uptake such as K+ channels, Ca2+ channels and ion exchangers. Revealing the mechanism of ion channels and transporters associated with nutrient uptake will be helpful to provide new methods to diagnosis and find potential targets for diseases like diabetes, inflammatory bowel diseases, etc. Even though some of study still remain ambiguous and in early stage, we believe that ion channels and transporters will be novel therapeutic targets in the future.

Function of TRP channels in monocytes/macrophages.

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium. These TRP channels may also intermingle with macrophage activation signals to jointly regulate the occurrence and development of diseases. Here, we summarize recent findings on the expression and function of TRP channels in macrophages and discuss their role as modulators of macrophage activation and function. As research on TRP channels in health and disease progresses, it is anticipated that positive or negative modulators of TRP channels for treating specific diseases may be promising therapeutic options for the prevention and/or treatment of disease.

Exploration of Converting Food Waste into Value-Added Products via Insect Pretreatment-Assisted Hydrothermal Catalysis.

The environmental burden of food waste (FW) disposal coupled with natural resource scarcity has aroused interest in FW valorization; however, transforming FW into valuable products remains a challenge because of its heterogeneous nature. In this study, a two-stage method involving black soldier fly (BSF)-based insect pretreatment and subsequent hydrothermal catalysis over a single-atom cerium-incorporated hydroxyapatite (Ce-HAP) was explored to convert FW into high added-value furfurals (furfural and 5-hydroxymethylfurfural). FW consisting of cereal, vegetables, meat, eggs, oil, and salt was initially degraded by BSF larvae to generate homogeneous BSF biomass, and then, crucial parameters impacting the conversion of BSF biomass into furfurals were investigated. Under the optimized conditions, 9.3 wt % yield of furfurals was attained, and repeated trials confirmed the recyclability of Ce-HAP. It was proved that the revenue of furfural production from FW by this two-stage method ranged from 3.14 to 584.4 USD/tonne. This study provides a potential technical orientation for FW resource utilization.

Up-regulation of cholesterol synthesis pathways and limited neurodegeneration in a knock-in Sod1 mutant mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder affecting brain and spinal cord motor neurons. Mutations in the copper/zinc superoxide dismutase gene ( SOD1 ) are associated with ∼20% of inherited and 1-2% of sporadic ALS cases. Much has been learned from mice expressing transgenic copies of mutant SOD1, which typically involve high-level transgene expression, thereby differing from ALS patients expressing one mutant gene copy. To generate a model that more closely represents patient gene expression, we created a knock-in point mutation (G85R, a human ALS-causing mutation) in the endogenous mouse Sod1 gene, leading to mutant SOD1 G85R protein expression. Heterozygous Sod1 G85R mutant mice resemble wild type, whereas homozygous mutants have reduced body weight and lifespan, a mild neurodegenerative phenotype, and express very low mutant SOD1 protein levels with no detectable SOD1 activity. Homozygous mutants exhibit partial neuromuscular junction denervation at 3-4 months of age. Spinal cord motor neuron transcriptome analyses of homozygous Sod1 G85R mice revealed up-regulation of cholesterol synthesis pathway genes compared to wild type. Transcriptome and phenotypic features of these mice are similar to Sod1 knock-out mice, suggesting the Sod1 G85R phenotype is largely driven by loss of SOD1 function. By contrast, cholesterol synthesis genes are down-regulated in severely affected human TgSOD1 G93A transgenic mice at 4 months. Our analyses implicate dysregulation of cholesterol or related lipid pathway genes in ALS pathogenesis. The Sod1 G85R knock-in mouse is a useful ALS model to examine the importance of SOD1 activity in control of cholesterol homeostasis and motor neuron survival. SIGNIFICANCE STATEMENT: Amyotrophic lateral sclerosis is a devastating disease involving the progressive loss of motor neurons and motor function for which there is currently no cure. Understanding biological mechanisms leading to motor neuron death is critical for developing new treatments. Using a new knock-in mutant mouse model carrying a Sod1 mutation that causes ALS in patients, and in the mouse, causes a limited neurodegenerative phenotype similar to Sod1 loss-of-function, we show that cholesterol synthesis pathway genes are up-regulated in mutant motor neurons, whereas the same genes are down-regulated in transgenic SOD1 mice with a severe phenotype. Our data implicate dysregulation of cholesterol or other related lipid genes in ALS pathogenesis and provide new insights that could contribute to strategies for disease intervention.

STDNet: Rethinking Disentanglement Learning With Information Theory.

Disentangled representation learning is typically achieved by a generative model, variational encoder (VAE). Existing VAE-based methods try to disentangle all the attributes simultaneously in a single hidden space, while the separation of the attribute from irrelevant information varies in complexity. Thus, it should be conducted in different hidden spaces. Therefore, we propose to disentangle the disentanglement itself by assigning the disentanglement of each attribute to different layers. To achieve this, we present a stair disentanglement net (STDNet), a stair-like structure network with each step corresponding to the disentanglement of an attribute. An information separation principle is employed to peel off the irrelevant information to form a compact representation of the targeted attribute within each step. Compact representations, thus, obtained together form the final disentangled representation. To ensure the final disentangled representation is compressed as well as complete with respect to the input data, we propose a variant of the information bottleneck (IB) principle, the stair IB (SIB) principle, to optimize a tradeoff between compression and expressiveness. In particular, for the assignment to the network steps, we define an attribute complexity metric to assign the attributes by the complexity ascending rule (CAR) that dictates a sequencing of the attribute disentanglement in ascending order of complexity. Experimentally, STDNet achieves state-of-the-art results in representation learning and image generation on multiple benchmarks, including Mixed National Institute of Standards and Technology database (MNIST), dSprites, and CelebA. Furthermore, we conduct thorough ablation experiments to show how the strategies employed here contribute to the performance, including neurons block, CAR, hierarchical structure, and variational form of SIB.