Recovery strategies and mechanisms of anammox reaction following inhibition by environmental factors: A review.

Anaerobic ammonium oxidation (anammox) is a promising biological method for treating nitrogen-rich, low-carbon wastewater. However, the application of anammox technology in actual engineering is easily limited by environmental factors. Considerable progress has been investigated in recent years in anammox restoration strategies, significantly addressing the challenge of poor reaction performance following inhibition. This review systematically outlines the strategies employed to recover anammox performance following inhibition by conventional environmental factors and emerging pollutants. Additionally, comprehensive summaries of strategies aimed at promoting anammox activity and enhancing nitrogen removal performance provide valuable insights into the current research landscape in this field. The review contributes to a comprehensive understanding of restoration strategies of anammox-based technologies.

Distinct roles of nuclear basket proteins in directing the passage of mRNA through the nuclear pore.

The in vivo characterization of the exact copy number and the specific function of each composite protein within the nuclear pore complex (NPC) remains both desirable and challenging. Through the implementation of live-cell high-speed super-resolution single-molecule microscopy, we first quantified the native copies of nuclear basket (BSK) proteins (Nup153, Nup50, and Tpr) prior to knocking them down in a highly specific manner via an auxin-inducible degron strategy. Second, we determined the specific roles that BSK proteins play in the nuclear export kinetics of model messenger RNA (mRNA) substrates. Finally, the three-dimensional (3D) nuclear export routes of these mRNA substrates through native NPCs in the absence of specific BSK proteins were obtained and further validated via postlocalization computational simulations. We found that these BSK proteins possess the stoichiometric ratio of 1:1:1 and play distinct roles in the nuclear export of mRNAs within live cells. The absence of Tpr from the NPC predominantly reduces the probability of nuclear mRNAs entering the NPC for export. Complete depletion of Nup153 and Nup50 results in an mRNA nuclear export efficiency decrease of approximately four folds. mRNAs can gain their maximum successful export efficiency as the copy number of Nup153 increased from zero to only half the full complement natively within the NPC. Lastly, the absence of Tpr or Nup153 seems to alter the 3D export routes of mRNAs as they pass through the NPC. However, the removal of Nup50 alone has almost no impact upon mRNA export route and kinetics.

Aberrant intrinsic functional brain networks in patients with functional constipation.

PURPOSE: Patients with functional constipation (FCon) often suffer from mental and psychological problems. To explore the possible neurological interaction, we used resting-state functional magnetic imaging (RS-fMRI) to compare the alterations in intrinsic brain functional networks at multiple levels between patients with FCon and healthy controls (HC). METHODS: Twenty-eight patients with FCon and twenty-nine HC were recruited for a series of examinations and RS-fMRI. Both graph theory analysis and functional connectivity (FC) analysis were used to investigate brain functional alterations between the two groups. Correlation analyses were performed among neuropsychological scores, clinical indexes, and neuroimaging data. RESULTS: Compared with the HC, the assortativity showed significantly increased in global level in patients with FCon. In regional level, we found obviously increased nodal degree and nodal efficiency in somatosensory network (SMN), decreased nodal degree, and increased nodal efficiency in default mode network (DMN) in the FCon group. Furthermore, FC analysis demonstrated several functional alterations within and between the networks, particularly including the SMN and visual network (VN) in sub-network and large-scale network analysis. Moreover, correlation analysis indicated that nodal metrics and aberrant FC among functional brain networks were associated with emotion and scores of constipation in patients with FCon. CONCLUSION: All these findings reflect the differences in intrinsic brain functional networks between FCon and HC. Our study highlighted SMN, DMN, and VN as critical network and may be involved in the neurophysiology of FCon, which may contribute to improve personalized treatment in patients with FCon.

A review of anammox metabolic response to environmental factors: Characteristics and mechanisms.

Anaerobic ammonium oxidation (anammox) is a promising low carbon and economic biological nitrogen removal technology. Considering the anammox technology has been easily restricted by environmental factors in practical engineering applications, therefore, it is necessary to understand the metabolic response characteristics of anammox bacteria to different environmental factors, and then guide the application of the anammox process. This review presented the latest advances of the research progress of the effects of different environmental factors on the metabolic pathway of anammox bacteria. The effects as well as mechanisms of conventional environmental factors and emerging pollutants on the anammox metabolic processes were summarized. Also, the role of quorum sensing (QS) mediating the bacteria growth, gene expression and other metabolic process in the anammox system were also reviewed. Finally, interaction and cross-feeding mechanisms of microbial communities in the anammox system were discussed. This review systematically summarized the variations of metabolic mechanism response to the external environment and cross-feeding interactions in the anammox process, which would provide an in-depth understanding for the anammox metabolic process and a comprehensive guidance for future anammox-related metabolic studies and engineering applications.

Microbial population changes and metabolic shift of candidatus accumulibacter under low temperature and limiting polyphosphate.

This study explored the microbial population dynamics of Accumulibacter (Acc) at low temperature and metabolic shift to limiting polyphosphate (Poly-P) in enhanced biological phosphorus removal (EBPR) system. The Accumulibacter-enriched EBPR systems, fed with acetate (HAc) and propionate (HPr) at 10 ± 1 °C respectively, were operated for 60 days in two identical SBR reactors (SBR-1 and SBR-2). The phosphorus removal performance in two systems was stable at 10 ± 1 °C, while the microbial community structure changed. Compared with the population structure in seed sludge, Accumulibacter clades reduced in the HAc system, while Acc I increased significantly in the HPr system. Low temperature was beneficial to the formation of granular sludge in the EBPR system, and the sludge granulation in the HAc system was more homogeneous than that in the HPr system. Accumulibacter in the HPr system can get ATP through glycogen accumulating metabolism (GAM) under limiting Poly-P condition at 10 ± 1 °C, while that in the HAc system cannot. This work suggests that poly-P levels can affect the metabolic pathway of Accumulibacter in EBPR systems under low temperature.

Fate of phthalates in a river receiving wastewater treatment plant effluent based on a multimedia model.

Phthalic acid esters (PAEs) can enter environment media by secondary effluent discharge from wastewater treatment plants (WWTP) into receiving rivers, thus posing a threat to ecosystem health. A level III fugacity model was established to simulate the fate and transfer of four PAEs in a study area in Tianjin, China, and to evaluate the influence of WWTP discharge on PAEs levels in the receiving river. The results show that the logarithmic residuals of most simulated and measured values of PAEs are within one order of magnitude with a good agreement. PAEs in the study area were mainly distributed in soil and sediment phases, which accounted for 84.66%, 50.26%, 71.96% and 99.09% for dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP), respectively. The upstream advection accounted for 77.90%, 93.20%, 90.21% and 90.93% of the total source of DMP, DEP, DBP and DEHP in the river water, respectively, while the contribution of secondary effluent discharge was much lower. Sensitivity analysis shows that emission and inflow parameters have greater influences on the multimedia distributions of PAEs than physicochemical and environmental parameters. Monte Carlo analysis quantifies the uncertainties and verifies the reliability of the simulation results.

Influence of thermal hydrolysis treatment on chemical speciation and bioleaching behavior of heavy metals in the sewage sludge.

In this study, the transformation of chemical speciation of Cr, Mn, As and Cd in the sewage sludge before and after thermal hydrolysis treatment was investigated using modified BCR method. The effect of thermal hydrolysis treatment and chemical speciation change on the subsequent bioleaching behavior was also researched. The results showed that the concentrations of Cr, Mn, As and Cd in oxidizable fraction decreased in the sludge treated by thermal hydrolysis. Meanwhile, the proportions of Cr, Mn and As in the mobile fractions (acid-soluble/exchangeable and reducible fraction) all decreased, while Cd was concentrated in the sludge treated by thermal hydrolysis. The final pH value of bioleached sludge treated by thermal hydrolysis was lower than that in the bioleached raw sewage sludge. And faster increase of oxidation-reduction potential (ORP) was also found in the bioleaching process of the sludge treated by thermal hydrolysis. The removal percentage of Mn and Cd increased in the bioleached sludge treated by thermal hydrolysis. Thermal hydrolysis treatment can promote the bioleaching to some extent. Furthermore, the environmental risk of Cr, Mn, As and Cd in the bioleached sludge treated by thermal hydrolysis was all alleviated according to risk assessment analysis compared with the bioleached raw sewage sludge.

Stability of pure oxygen aeration-activated sludge system under non-steady food-to-microorganism ratio conditions during petrochemical wastewater treatment.

This study investigates the stability of a pure oxygen aeration-activated sludge system for petrochemical wastewater treatment under high organic concentration and non-steady food-to-microorganism (F/M) ratio conditions. Sludge settling characteristics maintained relatively stable conditions with an F/M ratio variation from 0.15 ± 0.04 to 0.33 ± 0.07 kg COD/kg MLSS⋅d, while the excess F/M ratio (0.44 ± 0.16 kg COD/kg MLSS⋅d) resulted in deterioration of the organic removal and sludge-water separation performances. Loosely bound extracellular polymeric substances (EPS) showed more significant effect on sludge settleability than the tightly bound EPS. The genus Hydrogenophaga was related to organic removal performance, while Zoogloea and Chitinophaga were related to the effluent quality of suspended solids. The excess F/M ratio also caused an increase in Zoogloea and Chitinophaga, whereas the toxicity of petrochemical wastewater resulted in decreased abundance of Hydrogenophaga. These changes caused deterioration of the organic removal and sludge-water separation performances.

Start-up of single-stage partial nitritation-anammox micro-granules system: Performance and microbial community dynamics.

By manipulating influent nitrogen load and DO concentration in bulk liquid, the start-up and performance of a new micro-granule based partial nitritation-anammox process was investigated in a continuous stirred tank reactor (CSTR). Under the condition of nitrogen loadings from 0.3 to 1.4 kgN /m³/d and DO <0.21mg/L, the single-stage partial nitritation-anammox (SPNA) system was successfully started, with a nitrogen removal of 76.2%. Meanwhile, the oxygen utilization efficiency by ammonium oxidizing bacteria (AOB) increased in the system with the increase of influent ammonia loading rate. Micro-granules with an average diameter of 0.25 mm were formed. Sludge granulation was promoted by increasing influent nitrogen load, and there was a positive correlation between nitrogen load, extracellular polymeric substances (EPS) content and sludge particle size. Ca. Kuenenia became the dominant anaerobic ammonium oxidizing bacteria (AnAOB) in the SPNA system. As the dominant AOB genera, Nitrosomonas coexist with Ca. Kuenenia in the micro-granules.

Geochemical Signature of Natural Water Recharge in the Jungar Basin and Its Response to Climate.

This paper analyzed the physico-chemical characteristics of natural waters in a drainage system of the Jungar Basin, northwestern China to identify chemical evolution and recharge mechanisms of natural waters in an arid environment. The waters studied are different in mineralization, but are typically carbonate rivers and alkaline in nature. No Cl-dominated water type occurs, indicating an early stage of water evolution. Regolith and geomorphological parameters controlling ground-surface temperature may play a large role in the geological evolution of the water. Three main morphological and hydrological units are reflected in water physico-chemistry. Climate influences the salinization of natural waters substantially. Direct recharge from seasonal snow and ice-melt water and infiltration of rain to the ground are significant recharge processes for natural waters, but recharge from potential deep groundwater may be less important. The enrichment of ions in lakes has been mainly caused by evaporation rather than through the quality change of the recharged water.

Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1ß, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1ß and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder.

Vancomycin-loaded hydrogels with thermal-responsive, self-peeling, and sustainable antibacterial properties for wound dressing.

Wound dressings play an important role in wound healing. However, many wound dressings lack antibacterial properties and are difficult to remove from newly grown tissues, causing secondary wound injuries and repeated medical treatment. This study reports a new type of thermal-responsive hydrogel dressing consisting of vancomycin-loaded gelatin nanospheres (GNs) and poly((N-isopropylacrylamide)-co-N-(methylol acrylamide)) functional components that could impart self-peeling and sustainable antibacterial properties. SEM images showed that the prepared hydrogel possessed a porous microstructure and the homogeneous distribution of GNs in its network. Excellent swelling ratios and thermal-induced self-peeling characteristics were confirmed by qualitative analysis. The GNs not only enhanced the strain at break of the hydrogel, but also acted as drug carriers to slow down the drug release from the hydrogel, achieving sustainable antibacterial properties and balanced biocompatibility. Therefore, this vancomycin-loaded hydrogel with self-peeling characteristics provides an effective way of preventing wound infection and can be used as a novel platform for wide-ranging applications of wound dressings.

Add-on effects of Chinese herbal medicine external application (FZHFZY) to topical urea for mild-to-moderate psoriasis vulgaris: Protocol for a double-blinded randomized controlled pilot trial embedded with a qualitative study.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

Exploring Cellular Gateways: Unraveling the Secrets of Disordered Proteins within Live Nuclear Pores.

Understanding the spatial organization of nucleoporins (Nups) with intrinsically disordered domains within the nuclear pore complex (NPC) is crucial for deciphering eukaryotic nucleocytoplasmic transport. Leveraging high-speed 2D single-molecule tracking and virtual 3D super-resolution microscopy in live HeLa cells, we investigated the spatial distribution of all eleven phenylalanine-glycine (FG)-rich Nups within individual NPCs. Our study reveals a nuanced landscape of FG-Nup conformations and arrangements. Five FG-Nups are steadfastly anchored at the NPC scaffold, collectively shaping a central doughnut-shaped channel, while six others exhibit heightened flexibility, extending towards the cytoplasmic and nucleoplasmic regions. Intriguingly, Nup214 and Nup153 contribute to cap-like structures that dynamically alternate between open and closed states along the nucleocytoplasmic transport axis, impacting the cytoplasmic and nuclear sides, respectively. Furthermore, Nup98, concentrated at the scaffold region, extends throughout the entire NPC while overlapping with other FG-Nups. Together, these eleven FG-Nups compose a versatile, capped trichoid channel spanning approximately 270 nm across the nuclear envelope. This adaptable trichoid channel facilitates a spectrum of pathways for passive diffusion and facilitated nucleocytoplasmic transport. Our comprehensive mapping of FG-Nup organization within live NPCs offers a unifying mechanism accommodating multiple transport pathways, thereby advancing our understanding of cellular transport processes.

Association of social support with quality of life in patients with polyneuropathy.

The aim of this study was to examine the impact of social support on quality of life (QoL) in patients with polyneuropathy. One hundred and fifty-four patients with polyneuropathy were enrolled from a neuromuscular clinic. The QoL Instrument and the Medical Outcome Study-Social Support Survey (MOS-SSS) were used to assess QoL and social support, respectively. Disease severity and clinical factors were also assessed. Neuropathy patients had a lower QoL compared to a previously published normative sample (p < 0.0001) and an MOS-SSS comparable to other patients with chronic disease. Social support correlated weakly with the self esteem and emotional well being mental health dimensions (rs :0.20-0.38) but not the physical health QoL (PH-QoL) domains. Physical and mental QoL also correlated significantly with presence of pain (rs : -0.39 and -0.42, respectively) and number of autonomic symptoms (rs : -0.39 and -0.30, respectively). Social support independently predicts MH-QoL when controlling for age, gender, pain, and the Toronto Clinical Neuropathy Score (TCNS; p < 0.0001). TCNS and gender are independently related to PH-QoL (p < 0.05). This study demonstrates that improved social support serves as an independent predictor of MH-QoL when controlling for age, gender, pain, and severity of neuropathy. Future studies examining the effects of improving social support on QoL in patients with polyneuropathy are recommended.

Effect of Chinese herbal medicine injections for treatment of psoriasis vulgaris: a systematic review and meta-analysis.

Background: Psoriasis vulgaris (PV) is a longstanding, inflammatory, immune-responsive skin condition. Chinese herbal medicine injections (CHMIs) have been utilized for treating PV in Asian countries. This study aims to conduct a thorough systematic review and meta-analysis to comprehensively appraise the efficacy of CHMIs in treating PV. Methods: Seven databases were searched for randomized controlled trials that evaluated the effect of CHMIs in treating PV, ranging from 2004 to June 2022. The meta-analysis was undertaken based on outcome measures, treatment options, and treatment durations using Review Manager 5.4. The primary outcome measure of this study was a 60% or higher reduction in the Psoriasis Area and Severity Index score (PASI 60). A descriptive analysis was performed for the assessment of adverse events. Results: This systematic review incorporated 33 studies, comprising 3,059 participants. The main findings indicated significant differences based on the PASI 60 (RR = 1.30, 95% CI: 1.24 to 1.37, Z = 10.72, p < 0.00001), PASI 30 (RR = 1.25, 95% CI: 1.13 to 1.38, Z = 4.48, p < 0.00001), and PASI 20 (RR = 1.28, 95% CI: 1.13 to 1.45, Z = 3.82, p = 0.0001) outcome measures. Evaluating the treatment options, CHMIs in combination with monotherapies like narrowband ultraviolet B (NB-UVB) and the acitretin capsule (AC) showed a greater reduction in PASI 60 (RR = 1.33, 95% CI: 1.25 to 1.43, Z = 8.32, p < 0.00001). In terms of treatment duration, no significant difference was observed when the duration extended beyond 56 days. Furthermore, the results suggested that CHMIs might reduce the incidence of adverse events in the treatment of PV. Conclusion: This systematic review revealed preliminary clinical evidence supporting the use of CHMIs for treating PV, considering outcome measures, treatment options, and treatment durations. However, due to the low methodological quality and limited sample size of the included studies, there is an urgent need for high-quality, multi-center and larger-scale studies of CHMIs for PV to provide robust evidence for their clinical application. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326531], identifier [CRD42022326531].

The ciliary lumen accommodates passive diffusion and vesicle-assisted trafficking in cytoplasm-ciliary transport.

Transport of membrane and cytosolic proteins into the primary cilium is essential for its role in cellular signaling. Using virtual three-dimensional superresolution light microscopy, the movements of membrane and soluble proteins from the cytoplasm to the primary cilium were mapped. In addition to the well-characterized intraflagellar transport (IFT) route, we found two new pathways within the lumen of the primary cilium: passive diffusion and vesicle-assisted transport routes that are adopted by proteins for cytoplasm-cilium transport in live cells. Through these pathways, approximately half of IFT motors (KIF3A) and cargo (α-tubulin) take the passive diffusion route, and more than half of membrane-embedded G protein-coupled receptors (SSTR3 and HTR6) use RAB8A-regulated vesicles to transport into and inside primary cilia. Ciliary lumen transport is the preferred route for membrane proteins in the early stages of ciliogenesis, and inhibition of SSTR3 vesicle transport completely blocks ciliogenesis. Furthermore, clathrin-mediated, signal-dependent internalization of SSTR3 also occurs through the ciliary lumen. These transport routes were also observed in Chlamydomonas reinhardtii flagella, suggesting their conserved roles in trafficking of ciliary proteins.

A method for simulating spatial fates of chemicals in flowing lake systems: Application to phthalates in a lake.

In order to describe spatio-temporal distribution of chemicals in flowing lake systems, a dynamic multimedia fate model of chemicals with spatial differentiation was constructed by coupling the level IV fugacity model with lake hydrodynamics. It was successfully applied to four phthalates (PAEs) in a lake recharged by reclaimed water and its accuracy was verified. Results show that under the long-term influence of flow field, the distributions of PAEs in both lake water and sediment have significant spatial heterogeneity of 2∼5 orders of magnitude, but present different distribution rules, which was explained by analysis of PAE transfer fluxes. The spatial distribution of PAEs in the water column depends on hydrodynamic conditions and whether the primary source is reclaimed water or atmospheric input. Slow water exchange and flow speed promote the migration of PAEs from water to sediment, causing them to always accumulate in sediments far away from the recharging inlet. Uncertainty and sensitivity analysis show that the PAE concentrations in water phase are mainly affected by emission and physicochemical parameters, while those in sediment phase are also sensitive to environmental parameters. The model can provide important information and accurate data support for the scientific management of chemicals in flowing lake systems.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics.

BACKGROUND: Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. METHOD: We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. RESULTS: We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. CONCLUSION: In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.

North Atlantic subtropical mode water formation controlled by Gulf Stream fronts.

The North Atlantic Ocean hosts the largest volume of global subtropical mode waters (STMWs) in the world, which serve as heat, carbon and oxygen silos in the ocean interior. STMWs are formed in the Gulf Stream region where thermal fronts are pervasive and result in feedback with the atmosphere. However, their roles in STMW formation have been overlooked. Using eddy-resolving global climate simulations, we find that suppressing local frontal-scale ocean-to-atmosphere (FOA) feedback leads to STMW formation being reduced almost by half. This is because FOA feedback enlarges STMW outcropping, attributable to the mixed layer deepening associated with cumulative excessive latent heat loss due to higher wind speeds and greater air-sea humidity contrast driven by the Gulf Stream fronts. Such enhanced heat loss overshadows the stronger restratification induced by vertical eddies and turbulent heat transport, making STMW colder and heavier. With more realistic representation of FOA feedback, the eddy-present/rich coupled global climate models reproduce the observed STMWs much better than the eddy-free ones. Such improvement in STMW production cannot be achieved, even with the oceanic resolution solely refined but without coupling to the overlying atmosphere in oceanic general circulation models. Our findings highlight the need to resolve FOA feedback to ameliorate the common severe underestimation of STMW and associated heat and carbon uptakes in earth system models.