Mitotic spindle disassembly in human cells relies on CRIPT having hierarchical redox signals.

Swift and complete spindle disassembly in late mitosis is essential for cell survival, yet how it happens is largely unknown in mammalian cells. Here we used real-time live cell microscopy and biochemical assays to show that the primordial dwarfism (PD)-related cysteine-rich protein CRIPT dictates the spindle disassembly in a redox-dependent manner in human cells. This previously reported cytoplasmic protein was found to have a confined nuclear localization with a nucleolar concentration during interphase but was distributed to spindles and underwent redox modifications to form disulfide bonds in CXXC pairs during mitosis. Then, it directly interacted with, and might transfer a redox response to, tubulin subunits via a putative redox exchange among cysteine residues to induce microtubule depolymerization. Expression of CRIPT proteins with mutations of these cysteine residues blocked spindle disassembly, generating two cell types with long-lasting metaphase spindles or spindle remnants. Live-cell recordings of a disease-relevant mutant (CRIPTC3Y) revealed that microtubule depolymerization at spindle ends during anaphase and the entire spindle dissolution during telophase might share a common CRIPT-bearing redox-controlled mechanism.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson's disease.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson's disease (PD). It remains unclear whether and how basal ganglia nuclei, structures that are directly involved in the pathology of PD, are implicated in the occurrence of RBD. METHOD: Here, in parallel with whole-night video polysomnography, we recorded local field potentials from two major basal ganglia structures, the globus pallidus internus and subthalamic nucleus, in two cohorts of patients with PD who had varied severity of RBD. Basal ganglia oscillatory patterns during RBD and REM sleep without atonia were analysed and compared with another age-matched cohort of patients with dystonia that served as controls. RESULTS: We found that beta power in both basal ganglia nuclei was specifically elevated during REM sleep without atonia in patients with PD, but not in dystonia. Basal ganglia beta power during REM sleep positively correlated with the extent of atonia loss, with beta elevation preceding the activation of chin electromyogram activities by ~200 ms. The connectivity between basal ganglia beta power and chin muscular activities during REM sleep was significantly correlated with the clinical severity of RBD in PD. CONCLUSIONS: These findings support that basal ganglia activities are associated with if not directly contribute to the occurrence of RBD in PD. Our study expands the understanding of the role basal ganglia played in RBD and may foster improved therapies for RBD by interrupting the basal ganglia-muscular communication during REM sleep in PD.

Spatial transcriptomics reveals heterogeneity of macrophages in the tumor microenvironment of granulomatous slack skin.

Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma accompanied by an abundant number of macrophages and is clinically characterized by the development of pendulous skin folds. However, the characteristics of these macrophages in GSS remain unclear. Here, we conducted a spatial transcriptomic study on one frozen GSS sample and drew transcriptomic maps of GSS for the first time. Gene expression analysis revealed the enrichment of three clusters with macrophage transcripts, each exhibiting distinct characteristics suggesting that their primary composition consists of different subpopulations of macrophages. The CD163+ /CD206+ cluster showed a tumor-associated macrophage (TAM) M2-like phenotype and highly expressed ZFP36, CCL2, TNFAIP6, and KLF2, which are known to be involved in T-cell interaction and tumor progression. The APOC1+ /APOE+ cluster presented a non-M1 or -M2 phenotype and may be related to lipid metabolism. The CD11c+ /LYZ+ cluster exhibited an M1-like phenotype. Notably, these cells strongly expressed MMP9, MMP12, CHI3L1, CHIT1, COL1A1, TIMP1, and SPP1, which are responsible for extracellular matrix (ECM) degradation and tissue remodeling. This may partially explain the symptoms of cutaneous relaxation in GSS. Further immunohistochemistry on four GSS cases demonstrated that CD11c predominantly marked granulomas and multinucleated giant cells, whereas CD163 was mainly expressed on scattered macrophages, appearing as a mutually exclusive pattern. The expression pattern of MMP9 overlapped with that of CD11c, implying that CD11c+ macrophages may be a source of MMP9. Our data shed light on the characteristics of macrophages in the GSS microenvironment and provide a theoretical basis for the application of MMP9 inhibitors to prevent cutaneous relaxation of GSS. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Arsenic-Hyperaccumulator Pteris vittata Effectively Uses Sparingly-Soluble Phosphate Rock: Rhizosphere Solubilization, Nutrient Improvement, and Arsenic Accumulation.

Sparingly-soluble phosphate rock (PR), a raw material for P-fertilizer production, can be effectively utilized by the As-hyperaccumulator Pteris vittata but not most plants. In this study, we investigated the associated mechanisms by measuring dissolved organic carbon (DOC) and acid phosphatase in the rhizosphere, and nutrient uptake and gene expression related to the As metabolism in P. vittata. The plants were grown in a soil containing 200 mg kg-1 As and/or 1.5% PR for 30 days. Compared to the As treatment, the P. vittata biomass was increased by 33% to 4.6 g plant-1 in the As+PR treatment, corresponding to 27% decrease in its frond oxidative stress as measured by malondialdehyde. Due to PR-enhanced DOC production in the rhizosphere, the Ca, P, and As contents in P. vittata fronds were increased by 17% to 9.7 g kg-1, 29% to 5.0 g kg-1, and 57% to 1045 mg kg-1 in the As+PR treatment, thereby supporting its better growth. Besides, PR-induced rhizosphere pH increase from 5.0 to 6.9 promoted greater P uptake by P. vittata probably via upregulating low-affinity P transporters PvPTB1;1/1;2 by 3.7-4.1 folds. Consequently, 29% lower available-P induced the 3.3-fold upregulation of high-affinity P transporter PvPht1;3 in the As+PR treatment, which was probably responsible for the 58% decrease in available-As content in the rhizosphere. Consistent with the enhanced As translocation and sequestration, arsenite antiporters PvACR3/3;3 were upregulated by 1.8-4.4 folds in the As+PR than As treatment. In short, sparingly-soluble PR enhanced the Ca, P, and As availability in P. vittata rhizosphere and improved their uptake via upregulating genes related to As metabolism, suggesting its potential application for improving phytoremediation in As-contaminated soils.

Stable O3 Decomposition by Layered Double Hydroxides: The Pivotal Role of NiOOH Transformation.

Because ozone (O3) is a significant air pollutant, advanced O3 elimination technologies, particularly those under high-humidity conditions, have become an essential research focus. In this study, a nickel-iron layered double hydroxide (NiFe-LDH) was modified via intercalation with octanoate to develop an effective hydrophobic catalyst (NiFe-OAa-LDH) for O3 decomposition. The NiFe-OAa-LDH catalyst sustained its O3 decomposition rate of >98% for 48 h under conditions of 90% relative humidity, 840 L/(g·h) space velocity, and 100 ppm inlet O3 concentration. Moreover, it maintained a decomposition rate of 90% even when tested at a higher airflow rate of 2500 L/(g·h). Based on the changes induced by the Ni-OII to Ni-OIII bonds in NiFe-OAa-LDH during O3 treatment, catalytic O3 decomposition was proposed to occur in two stages. The first stage involved the reaction between the hydroxyl groups and O3, leading to the breakage of the O-H bonds, formation of NiOOH, and structural changes in the catalyst. This transformation resulted in the formation of abundant and stable hydrogen vacancies. According to density functional theory calculations, O3 can be effectively decomposed at the hydrogen vacancies with a low energy barrier during the second stage. This study provides new insights into O3 decomposition.

Impacts of inflammatory cytokines on depression: a cohort study.

BACKGROUND: Inflammatory factors are associated with depression. We seek to investigate the correlation between inflammatory cytokines and prognosis of depression or suicidal ideation and behavior at 3 months in depression patients. METHODS: Eighty-two depressed outpatients were recruited and treated as usual. Plasma cytokines were measured at baseline. Patients were followed up with Patient Health Questionnaire-9 and suicidal ideation and behavior according to the item 3 of Hamilton depression scale for 3 months. RESULTS: Compared to the depression patients with low level of interleukin-1ß, the high one had severe depressive symptoms at month 2 and 3 (B 0.92, P < 0.01; B 0.86, P = 0.02; respectively). The incidence of suicidal ideation or behavior was 18.3% at 3 months. Depression patients with high levels of tumor necrosis factor-α showed high risk of suicidal ideation and behavior than the low one (OR 2.16, 95% CI 1.00-4.65, P = 0.04). CONCLUSIONS: High levels of interleukin-1ß and tumor necrosis factor-α were predictive of middle-term severe depressive symptoms and suicidal ideation and behavior respectively.

Identification of sources and analysis of spatial distribution of soil heavy metals in northern China coal mining areas.

The mining and utilization of coal resources has not only promoted rapid economic development but also poses a potential threat to the ecological environment. The purpose of this study is to clarify the effects both of mining and land use types on the spatial distribution and particular sources of heavy metals in soil, using inverse distance weighted (IDW) and the Positive Matrix Factorization (PMF) model. A total of 99 topsoil and profile soil samples across different land use types and mining conditions were collected. The contamination of soil with Cd, Pb, and Hg in the research area was most severe, with the coefficient of variation (CV) of Hg being the largest, while also being heavily influenced by human activities. Severely polluted regions were mainly distributed in the center of the coal mining area, as well as near the highway. The contents of heavy metals for various land use patterns were ranked as follows: forestland > farmland > bare land > grassland > building land. Hg, Cd, Pb, Cr, and Zn had showed migration in the 0-60 cm depth range, and the enrichment factors (EFs) of Cd, Pb, Hg, and As in the soil profile were the most significant. The PMF demonstrated that the contributions of industrial activities and atmospheric deposition, transportation and mining activities, agricultural activities, and natural sources accounted for 31.25%, 28.13%, 22.24%, and 18.38%, respectively. The migration and deposition of atmospheric particulate matter from coal mining, transportation, and coal combustion under winds triggered heavy metal contamination in semi-arid areas of northern China. This phenomenon has important implications for the prevention and reduction of heavy metal pollution through various effective measures in coal-mining cities in northern China.

Identification of Direct Anchoring Sites for Monoatomic Dispersion of Precious Metals (Pt, Pd, Ag) on CeO2 Support.

Monoatomic dispersion of precious metals on the surface of CeO2 nanocrystals is a highly practical approach for dramatically reducing the usage of precious metals while exploiting the unique properties of single-atom catalysts. However, the specific atomic sites for anchoring precious metal atoms on the CeO2 support and underlying chemical mechanism remain partially unknown. Herein, we show that the terminal hydroxyls on the (100) surface are the most stable sites for anchoring Ag atoms on CeO2 , indicating that CeO2 nanocubes are the most efficient substrates to achieve monoatomic dispersion of Ag. Importantly, the newly identified chemical mechanism for single-metal-atom dispersion on CeO2 nanocubes appears to be generic and can thus be extended to other precious metals (Pt and Pd). In fact, our experiments also show that atomically dispersed Pt/Pd species exhibit morphology- and temperature-dependent CO selectivity in the catalytic CO2 hydrogenation reaction.

Programmable optical switching integrated chip for 4-bit binary true/inverse/complement code conversions based on fluorinated photopolymers.

In this work, programmable optical switching integrated chips for 4-bit binary true/inverse/complement optical code conversions (OCCs) are proposed based on fluorinated photopolymers. Fluorinated bis-phenol-A novolac resin (FAR) with low absorption loss and fluorinated polyacrylate (FPA) with high thermal stability are self-synthesized as core and cladding layer, respectively. The basic architecture of operating unit for the photonic chip designed is composed of directional coupler Mach-Zehnder interferometer (DC-MZI) thermo-optic (TO) switching, X-junction, and Y-bunching waveguide structures. The waveguide module by cascading 16 operating units could realize OCCs function through optical transmission matrix. The response time of the 4-bit binary OCCs is measured as about 300 µs. The insertion loss and extinction ratio of the actual chip are obtained as about 10.5 dB and 15.2 dB, respectively. The electric driving power consumption for OCCs is less than 6 mW. The true/inverse/complement OCCs are achieved by the programmable modulation circuit. The proposed technique is suitable for achieving optical digital computing system with high-speed signal processing and low power consumption.

Triple-layered optical interconnecting integrated waveguide chip based on epoxy cross-linking fluorinated polymer photonic platform.

In this study, a triple-layered optical interconnecting integrated waveguide chip was designed and fabricated using an epoxy cross-linking polymer photonic platform. Fluorinated photopolymers FSU-8 and AF-Z-PC EP were self-synthesized as waveguide cores and cladding materials, respectively. The triple-layered optical interconnecting waveguide device comprised 4 × 4 arrayed waveguide grating (AWG) -based wavelength-selective switching (WSS) arrays, 4 × 4 multi-mode interference (MMI) -cascaded channel-selective switching (CSS) arrays, and 3 × 3 direct-coupling (DC) interlayered switching arrays. The overall optical polymer waveguide module was fabricated by direct UV writing. For the multilayered WSS arrays, the wavelength-shifting sensitivity was ∼0.48 nm/°C. For the multilayered CSS arrays, the average switching time was ∼280 µs, and the maximum power consumption was <30 mW. For interlayered switching arrays, the extinction ratio approximated 15.2 dB. The transmission loss for the triple-layered optical waveguide chip was measured as 10.0-12.1 dB. The flexible multilayered photonic integrated circuits (PIC) can be used in high-density integrated optical interconnecting systems with a large-volume optical information transmission capacity.

Living alone and health-related quality of life among adults with obstructive sleep apnea in a single-center cohort study.

OBJECTIVE: To determine the impact of a solitary lifestyle on health-related quality of life (HRQoL) in adults with obstructive sleep apnea (OSA). METHODS: This was a prospective cohort study; patients diagnosed with OSA but not receiving continuous positive airway pressure (CPAP) therapy were enrolled in our study. These participants completed basic information and the Short Form-36 Health Survey (SF-36) at baseline and were divided into the living alone and living with others groups. Telephone follow-up was performed 1 year later to re-evaluate the SF-36. Differences in health status between and within groups were assessed. In addition, variables associated with changes in the health of the whole population were examined. RESULTS: A total of 402 patients with OSA were enrolled, including 120 in the living alone group and the rest in the living with others group. After a year, mental health scores of the living alone group decreased (55.7 ± 21.5 versus 54.1 ± 22.7, p = 0.001), while physical functioning scores of the living with others group increased significantly (82.1 ± 24.7 versus 82.6 ± 24.2, p = 0.006). In the whole population, the determinants of mental health change after 1 year from baseline were alcohol drinking (beta coefficient - 1.169, 95% CI - 2.03 to - 0.309, p = 0.008) and solitary living (beta coefficient - 1.135, 95% CI - 2.072 to - 0.199, p = 0.018). CONCLUSION: Regarding all initial variables, alcohol drinking and solitary living seem to be the predictors of mental health change of patients with OSA in China. We speculate that to improve the quality of life of such people, the medical staff could provide certain social support for them.

Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study.

RATIONALE: Using latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA. METHODS: LCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTs, were evaluated in EARLI and VALID with LCA-derived subphenotypes as the gold-standard. RESULTS: A 2-class model best fit the population in VALID (p=0.0010) and in EARLI (p<0.0001). Class 2 comprised 27% and 37% of the populations in VALID and EARLI, respectively. Consistent with the previously described 'hyperinflammatory' subphenotype, Class 2 was characterised by higher proinflammatory biomarkers, acidosis and increased shock and worse clinical outcomes. The similarities between these and prior RCT-derived subphenotypes were further substantiated by the performance of the parsimonious classifier models in both cohorts (area under the curves 0.92-0.94). The hyperinflammatory subphenotype was associated with increased prevalence of chronic liver disease and neutropenia and reduced incidence of chronic obstructive pulmonary disease. Measurement of novel biomarkers showed significantly higher levels of matrix metalloproteinase-8 and markers of endothelial injury in the hyperinflammatory subphenotype, whereas, matrix metalloproteinase-9 was significantly lower. CONCLUSION: Previously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.

An extinct and deeply divergent tiger lineage from northeastern China recognized through palaeogenomics.

Tigers (Panthera tigris) are flagship big cats and attract extensive public attention due to their charismatic features and endangered status. Despite this, little is known about their prehistoric lineages and detailed evolutionary histories. Through palaeogenomic analyses, we identified a Pleistocene tiger from northeastern China, dated to beyond the limits of radiocarbon dating (greater than 43 500 years ago). We used a simulated dataset and different reads processing pipelines to test the validity of our results and confirmed that, in both mitochondrial and nuclear phylogenies, this ancient individual belongs to a previously unknown lineage that diverged prior to modern tiger diversification. Based on the mitochondrial genome, the divergence time of this ancient lineage was estimated to be approximately 268 ka (95% CI: 187-353 ka), doubling the known age of tigers' maternal ancestor to around 125 ka (95% CI: 88-168 ka). Furthermore, by combining our findings with putative mechanisms underlying the discordant mito-nuclear phylogenetic placement for the South China tigers, we proposed a more complex scenario of tiger evolution that would otherwise be missed using data from modern tigers only. Our study provides the first glimpses of the genetic antiquity of tigers and demonstrates the utility of aDNA-based investigation for further understanding tiger evolution.

Interlayer directional coupling thermo-optic waveguide switches based on functionalized epoxy-crosslinking polymers.

In this study, interlayer directional coupling (DC) thermo-optic (TO) waveguide switches were designed and fabricated using functionalized epoxy-crosslinking polymers. Fluorinated SU-8 (FSU-8) with a photo-initiating epoxy-crosslinking network was self-synthesized as a waveguide core material. A copolymer of methyl methacrylate and glycidyl methacrylate P(MMA-co-GMA) with a thermo-initiating epoxy crosslinking structure was self-synthesized as a waveguide cladding material. Compared with commercial pure SU-8 and PMMA, FSU-8 exhibited a lower absorption loss and P(MMA-co-GMA) exhibited a higher thermal stability. Using epoxy-crosslinking functionalized polymers, the structure of the waveguides and electrode heaters were optimized, and the performance parameters of the interlayer DC TO switches were simulated. At a signal wavelength of 1550 nm, the insertion loss, extinction ratio, and power consumption of the actual interlayer devices were measured as 6.7 dB, 15.6 dB, and 9 mW, respectively. The rising and falling response times of the TO switches were obtained as 631.6 µs and 362 µs, respectively. The self-leveling ability and solvent resistance characteristic of the epoxy-crosslinking network for FSU-8 and P(MMA-co-GMA) may guarantee the realization of interlayer DC TO waveguide switches. The proposed technique will be suitable for photonic integrated waveguide chips with multilayer stacking dynamic optical information interactions.

Metal-printing tunable interlayer waveguide coupler using low-loss fluorinated polycarbonate.

Tunable three-dimensional (3D) integrated optical waveguide chips with optical interconnection function are beneficial to expand the application of optical devices in a 3D integrated photonic module. Here, we propose a thermo-optic (TO) tunable interlayer waveguide coupler based on the metal-printing technique. Low-loss fluorinated polycarbonate (AF-Ali-PC MA) and poly (methyl methacrylate-glycidyl methacrylate) [P(MMA-co-GMA)] are synthesized as waveguide core and cladding layer, respectively. The thermal stability and optical adsorption characteristics of AF-Ali-PC MA are analyzed. Optical signal transmission features of the interlayer coupling waveguides are simulated. The optical response properties and fabrication process flows of a dynamic multilayer waveguide chip can be greatly improved by the metal-printing technique. The on-off time of the TO interlayer coupling chip is obtained as 250 µs, and the electrical power consumption is measured as 7.6 mW. To the best of our knowledge, this is the first time that a TO tunable interlayer waveguide coupler is achieved by an efficient metal-printing method, which is suitable for large-scale photonic integrated circuit (PIC) systems and multilayer optical interconnection (OXC) networks.

COVID-19 pandemic: study on simple, easy, and practical relaxation techniques while wearing medical protective equipment.

BACKGROUND: No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment. METHODS: This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance. RESULTS: Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6). CONCLUSION: Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.

Both Ends of Values in the Hemoglobin Spectrum Are Associated with Adverse Stroke Outcomes.

BACKGROUND AND PURPOSE: Existing studies on the association between hemoglobin values and stroke outcomes mostly focus on the lower side and mortality, often the only and primary endpoint. The current study was conducted to assess the association between hemoglobin concentration and a variety of poor stroke outcomes in patients with acute ischemic stroke. METHODS: We studied 8,321 patients enrolled in the China National Stroke Registry (CNSR) between 2007 and 2008. Patients were divided into 7 groups, and a logistic regression model was used to evaluate the association. Endpoints of interest included 1-year all-cause mortality, stroke recurrence, combined endpoint, and stroke disability. Stroke disability was defined as a modified Rankin Scale of 2-6. RESULTS: Patients with low and high hemoglobin values (≤11.6 g/dL and >16.1 g/dL) had higher proportion of poststroke adverse events than those in other groups. As compared with the fourth group of hemoglobin values of 13.5-14.2 g/dL, the adjusted odds ratios (ORs) with 95% confidence interval (CI) of low hemoglobin values (≤11.6 g/dL) were 2.25 (1.72-2.93) for all-cause mortality, 1.30 (1.04-1.61) for stroke recurrence, 1.63 (1.33-2.01) for combined endpoint, and 1.37 (1.12-1.67) for stroke disability, respectively. And, the ORs of high hemoglobin values (>16.1 g/dL) for adverse stroke outcomes were 1.72 (1.25-2.37), 1.43 (1.13-1.82), 1.43 (1.13-1.81), and 1.31 (1.06-1.63), respectively. Stratified analysis showed significant interactions between sex and categories of hemoglobin values for all-cause mortality (p = 0.05), stroke recurrence (p = 0.03), and combined endpoint (p = 0.01) but not for stroke disability (p = 0.24). CONCLUSIONS: Our study found both low and high hemoglobin values were associated with adverse stroke outcomes including all-cause mortality, stroke recurrence, combined endpoint, and stroke disability, which showed a U-shaped association. And, significant interactions between sex and hemoglobin concentration on all-cause mortality and stroke recurrence were also identified.

Quantitative analysis of nutrients for nucleosides, nucleobases, and amino acids hidden behind five distinct regions-derived Poria cocos using ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry.

Poria cocos is an edible fungus used as a health product and traditional Chinese medicinal preparation. Nevertheless, little is known about its nutrients. In this study, ultra-high performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry was conducted to quantify nucleosides, nucleobases, and amino acids in 32 batches of Poria cocos samples collected from Anhui, Sichuan, Hubei, Hunan, and Guizhou. Subsequently, the linearity, precision, repeatability, stability, and recovery of our methods were validated. Samples from different regions were clearly separated by partial least squares discriminant analysis and cluster analysis. Our results suggested that Poria cocos samples from different geographical environments differed in nucleosides, nucleobases, and amino acids. The plot of variable importance for projection disclosed differential compositions of L-Leucine, Uridine, L-Asparagine, L-Glutamine, L-phenylalanine, L-Ornithine monohydrochloride, L-Hydroxyproline, Taurine, and Inosine in Poria cocos from five regions. We found the highest content of total analytes, total amino acids, and total non-essential amino acids in Poria cocos from Anhui, total essential amino acids in the Sichuan samples, and total nucleosides in the Hunan samples. Overall, we determined the content of Poria cocos-derived nucleosides, nucleobases, and amino acids, providing the foothold for further chemical mining and use of Poria cocos.

Efficacy of Shuganjieyu capsule for treatment of neurologic disorders combined with depression: A meta-analysis.

Shuganjieyu capsule (SGJY) is the first Chinese herbal medicine approved for treatment of depression; however, the Shuganjieyu capsule efficacy in patients with neurologic disorders combined with depression remains to be determined. Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other electronic databases were searched to obtain relevant studies through May 2019. Newcastle-Ottawa and Jadad scales are used for the quality assessed. Sensitivity analysis, subgroup analysis and meta-regression were performed to evaluate sources of heterogeneity. Sixty-seven studies were selected for further analysis. Patients who had Shuganjieyu therapy had a higher effective rate and lower Hamilton Depression Rating Scale (HAM-D) score compared to patients who had non-shuganjieyu therapy. In addition, Shuganjieyu capsule improve symptoms of patients with stroke (National Institutes of Health Stroke Scale (NIHSS) score: Weighted mean difference (WMD)= -2.64; 95% CI: -3.95 to -1.33; P<0.001), Parkinson's disease score: WMD= -2.53; 95% CI: -3.92 to -1.14; P<0.001), and sleep disorders (Pittsburgh Sleep Quality Index (PSQI) score: WMD= -4.97; 95% CI: -7.56 to -2.38; P<0.001). Our results demonstrated that there were clinical benefits for patients with neurologic disorders after Shuganjieyu capsule therapy compared with non-shuganjieyu therapy with respect to effective rate and HAM-D, NIHSS, UPDRS and PSQI scores.

Targeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-κB Signaling Pathway in Sepsis.

Neuropilin-1 (Nrp-1) contributes to maintaining the stability of CD4+ CD25+ regulatory T cells (Tregs). We investigated the impact of Nrp-1 on the stability of CD4+ CD25+ Tregs, and the underlying signaling pathways, in a model of sepsis. Splenic CD4+ CD25+ Tregs were either treated with anti-Nrp-1, transfected to silence Nrp-1 and inhibitor of NF-κB kinase subunit beta (IKKß), or administered ammonium pyrrolidine dithiocarbamate (PDTC), followed by recombinant semaphorin 3A (rSema3A), in a simulation of sepsis. After the creation of a sepsis model in mice, anti-Nrp-1 was administered. The expression of the gene encoding forkhead box protein P-3 foxp3-Treg-specific demethylated region (foxp3-TSDR), the apoptosis rate, the expression of Foxp-3, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and transforming growth factor ß1 (TGF-ß1), interleukin 10 (IL-10) and TGF-ß1 secretion, and the NF-κB signaling activity of CD4+ CD25+ Tregs were determined. Sepsis simulation with or without rSema3A increased the stability of CD4+ CD25+ Tregs, including an increase in the expression of Foxp-3, CTLA-4, and TGF-ß1, decreases in apoptosis and the methylation of foxp3-TSDR, increases in the secretion of TGF-ß1 and IL-10, and an increase in the immunosuppressive effect on CD4+ T lymphocytes. Silencing of Nrp-1 or anti-Nrp-1 treatment abrogated lipopolysaccharide (LPS) stimulation with or without an rSema3A-mediated effect. Sepsis simulation increased the DNA-binding activity of NF-κB, as well as the ratios of phosphorylated IKKß (p-IKKß) to IKKß and p-P65 to P65 in vitro and vivo Silencing of IKKß expression or PDTC treatment suppressed the stability of CD4+ CD25+ Tregs in LPS-induced sepsis. Weakening Nrp-1 reduced the stability of CD4+ CD25+ Tregs by regulating the NF-κB signaling pathway; thus, Nrp-1 could be a new target for immunoregulation in sepsis.