Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

Effects of staged multiple phytohormones application on capillary-driven attached Chlorella sp. biofilm.

Comparing with single phytohormone application, applying multiple phytohormones to microalgae-based wastewater treatment systems can offer more extensive growth-promoting and stress-protecting effects for microalgae, yet the advantage of stress-relieving salicylic acid (SA) under combined phytohormones application scenario has not been exploited. Employing the improved capillary-driven attached microalgae culturing device (CD-PBR) previously used for single phytohormone application, this study compared the effects of mixed and single phytohormone(s) addition under as low as 10-7 M dosage. In order to make the best of SA for its stress-relieving property, postponed SA addition combined with applying other phytohormone(s) at the beginning of microalgae cultivation was also investigated. Combination of 10-6 M 6-benzylaminopurine (6-BA) with 10-7 M SA was sufficient for enhancing growth-promoting effects and anti-oxidative responses for attached Chlorella sp., while indole-3-acetic acid (IAA) addition was unnecessary. Combination of 6-BA addition at the beginning while postponed SA addition on Day 4 could further sustain such beneficial effects, while removing up to 99.7% total nitrogen (TN) and 97.9% total phosphorus (TP) from the bulk liquid. These results provided innovative strategies on mixed phytohormones addition for microalgae.

Insights into aggregation dynamics of NACore peptides from coarse-grained simulations.

Alpha(α)-synuclein is closely related to the pathogenesis of Parkinson's disease (PD). The NACore, a fragment of α-synuclein, is considered to be the key region of α-synuclein that causes PD. The aggregation dynamics of NACores are studied via coarse-grained molecular dynamics simulations. We find that NACores can self-assemble into a large cluster at high concentrations. The aggregation dynamics can be divided into three stages. The growth kinetics for the first and second stages follows the power law, Smax ~ tγ , with the second stage faster than the first one. The characteristic lifetime for the high concentration is 40 times larger than that for the low concentration, implying the low fluidity. Understanding the aggregation dynamics of NACores is helpful to develop drugs for therapeutic prevention and intervention.

The Modified Rectangle Flap Epicanthoplasty: A Novel and Individualized Design.

BACKGROUND: The epicanthal fold is ordinary in the eyelids of Asians, and the aesthetic appearance of eyelid surgery could be reduced and undermined; thus, medial epicanthoplasty is commonly performed to eliminate the effect of the epicanthal fold with less scarring. At present, there are a lot of techniques that have been described for the treatment of epicanthal fold. The potential problems, however, such as visible scar or under correction in the medial canthus area are challenges to surgeons. The purpose of our study was to explore a novel and individualized design using a modified rectangle flap with acceptable functional and aesthetic outcomes. METHODS: From January 2017 to January 2018, epicanthoplasty was performed for 40 patients by using a modified rectangle flap. All patients underwent double-eyelid surgery at the same time when they needed it. The evaluation criteria included the intercanthal distance (ICD), interpupillary distance (IPD), the ratio of ICD to IPD (ICD ratio), scar visibility, and cosmetic results. RESULTS: From January 2017 to January 2018, the modified rectangle flap method was carried out on 40 patients, who were evaluated at follow-up from 7 to 15 months. The average intercanthal length was 36.9 ± 2.2 mm preoperatively and decreased significantly to 31.5 ± 1.8 mm postoperatively, 7 months after the surgery (P < 0.01). The excellent cosmetic results, in terms of an open medial canthus, were observed during follow-up periods, with no definite recurrence, hypertrophic scar, or injury of the lacrimal apparatus. The inner canthus and lacrimal caruncle are fully exposed with an invisible scar. Both the patients and the surgeon judged that the aesthetic outcomes were excellent or good. CONCLUSIONS: This modified rectangular flap is an effective and personalized method of correcting the medial folds that leave no additional scar in the medial canthal area, and the procedure meets the patient's aesthetic expectations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart.

Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart. This contractile dysfunction is associated with impaired oxidative decarboxylation of α-ketoglutarate, a redirection of Krebs cycle intermediates, and increased ATP citrate lyase (ACL) activity. Increased availability of D2-HG also leads to altered histone methylation and acetylation in the heart. We propose that D2-HG promotes cardiac dysfunction by impairing α-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner. Collectively, our results highlight the impact of cancer cell metabolism on function and metabolism of the heart.

MiR-362-5p as a novel prognostic predictor of cytogenetically normal acute myeloid leukemia.

BACKGROUND: MicroRNAs are of special interest in cancer research and hold significant promise as diagnostic and prognostic biomarkers for malignant disease. MiR-362-5p have been found to exert both oncogenic and tumor suppressive effects depending highly on the cellular context. The aim of this study was to determine whether the expression of miR-362-5p can be served as a prognostic factor for patients with cytogentically normal acute myeloid leukemia (CN-AML). METHODS: We enrolled 224 patients with CN-AML and measured the expression of miR-362-5p by quantitative real time PCR analysis. We classified patients into high and low expression based on the median value. The Cox regression analyses were carried out to assess the prognostic significance of miR-362-5p expression in the context of the well-established predictors. Additionally, microRNA expression profiling were conducted to identify the biological insights between high and low group. RESULTS: High expressers had older age. High expressers obtained shorter overall survival in the univariate analysis. The independent prognostic value of miR-362-5p remained in the context of the well-established clinical and cytogenetic predictors. Moreover, the prognostic value of miR-362-5p was also validated in an independent cohort of CN-AML. Notably, numerous oncomiRs were also high expressed in high miR-362-5p group. CONCLUSION: High miR-362-5p expression was associated with poorer overall survival implicating the oncogenic function in AML development.

Microalgae-based advanced municipal wastewater treatment for reuse in water bodies.

Reuse of secondary municipal effluent from wastewater treatment plants in water bodies could effectively alleviate freshwater resource shortage. However, excessive nutrients must be efficiently removed to prevent eutrophication. Compared with other means of advanced wastewater treatment, microalgae-based processes display overwhelming advantages including efficient and simultaneous N and P removal, no requirement of additional chemicals, O2 generation, CO2 mitigation, and potential value-added products from harvested biomass. One particular challenge of microalgae-based advanced municipal wastewater treatment compared to treatment of other types of wastewater is that concentrations of nutrients and N:P ratios in secondary municipal effluent are much lower and imbalanced. Therefore, there should be comprehensive considerations on nutrient removal from this specific type of effluent. Removal of nutrients and organic substances, and other environmental benefits of microalgae-based advanced municipal wastewater treatment systems were summarized. Among the existing studies on microalgal advanced nutrient removal, much information on major parameters is absent, rendering performances between studies not really comparable. Mechanisms of microalgae-based nitrogen and phosphorus removal were respectively analyzed to better understand advanced nutrient removal from municipal secondary effluent. Factors influencing microalgae-based nutrient removal were divided into intrinsic, environmental, and operational categories; several factors were identified in each category, and their influences on microalgal nutrient removal were discussed. A multiplicative kinetic model was integrated to estimate microalgal growth-related nutrient removal based majorly on environmental and intrinsic factors. Limitations and prospects of future full-scale microalgae-based advanced municipal wastewater treatment were also suggested. The manuscript could offer much valuable information for future studies on microalgae-based advanced wastewater treatment and water reuse.

A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value.

Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and tricarboxylic [corrected] acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML.

Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib.

Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells.

High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.

The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML.

Seawater Chlorella sp. biofilm for mariculture effluent polishing under environmental combined antibiotics exposure and ecological risk evaluation based on parent antibiotics and transformation products.

Mariculture effluent polishing with microalgal biofilm could realize effective nutrients removal and resolve the microalgae-water separation issue via biofilm scraping or in-situ aquatic animal grazing. Ubiquitous existence of antibiotics in mariculture effluents may affect the remediation performances and arouse ecological risks. The influence of combined antibiotics exposure at environment-relevant concentrations towards attached microalgae suitable for mariculture effluent polishing is currently lack of research. Results from suspended cultures could offer limited guidance since biofilms are richer in extracellular polymeric substances that may protect the cells from antibiotics and alter their transformation pathways. This study, therefore, explored the effects of combined antibiotics exposure at environmental concentrations towards seawater Chlorella sp. biofilm in terms of microalgal growth characteristics, nutrients removal, anti-oxidative responses, and antibiotics removal and transformations. Sulfamethoxazole (SMX), tetracycline (TL), and clarithromycin (CLA) in single, binary, and triple combinations were investigated. SMX + TL displayed toxicity synergism while TL + CLA revealed toxicity antagonism. Phosphorus removal was comparable under all conditions, while nitrogen removal was significantly higher under SMX and TL + CLA exposure. Anti-oxidative responses suggested microalgal acclimation towards SMX, while toxicity antagonism between TL and CLA generated least cellular oxidative damage. Parent antibiotics removal was in the order of TL (74.5-85.2 %) > CLA (60.8-69.5 %) > SMX (13.5-44.1 %), with higher removal efficiencies observed under combined than single antibiotic exposure. Considering the impact of residual parent antibiotics, CLA involved cultures were identified of high ecological risks, while medium risks were indicated in other cultures. Transformation products (TPs) of SMX and CLA displayed negligible aquatic toxicity, the parent antibiotics themselves deserve advanced removal. Four out of eight TPs of TL could generate chronic toxicity, and the elimination of these TPs should be prioritized for TL involved cultures. This study expands the knowledge of combined antibiotics exposure upon microalgal biofilm based mariculture effluent polishing.

Effects of environmental microplastic exposure on Chlorella sp. biofilm characteristics and its interaction with nitric oxide signaling.

Microalgal biofilm is promising in simultaneous pollutants removal, CO2 fixation, and biomass resource transformation when wastewater is used as culturing medium. Nitric oxide (NO) often accumulates in microalgal cells under wastewater treatment relevant abiotic stresses such as nitrogen deficiency, heavy metals, and antibiotics. However, the influence of emerging contaminants such as microplastics (MPs) on microalgal intracellular NO is still unknown. Moreover, the investigated MPs concentrations among existing studies were mostly several magnitudes higher than in real wastewaters, which could offer limited guidance for the effects of MPs on microalgae at environment-relevant concentrations. Therefore, this study investigated three commonly observed MPs in wastewater at environment-relevant concentrations (10-10,000 µg/L) and explored their impacts on attached Chlorella sp. growth characteristics, nutrients removal, and anti-oxidative responses (including intracellular NO content). The nitrogen source NO3--N at 49 mg/L being 20 % of the nitrogen strength in classic BG-11 medium was selected for MPs exposure experiments because of least intracellular NO accumulation, so that disturbance of intracellular NO by nitrogen availability could be avoided. Under such condition, 10 µg/L polyethylene (PE) MPs displayed most significant microalgal growth inhibition comparing with polyvinyl chloride (PVC) and polyamide (PA) MPs, showing extraordinarily low chlorophyll a/b ratios, and highest superoxide dismutase (SOD) activity and intracellular NO content after 12 days of MPs exposure. PVC MPs exposed cultures displayed highest malonaldehyde (MDA) content because of the toxic characteristics of organochlorines, and most significant correlations of intracellular NO content with conventional anti-oxidative parameters of SOD, CAT (catalase), and MDA. MPs accelerated phosphorus removal, and the type rather than concentration of MPs displayed higher influences, following the trend of PE > PA > PVC. This study expanded the knowledge of microalgal biofilm under environment-relevant concentrations of MPs, and innovatively discovered the significance of intracellular NO as a more sensitive indicator than conventional anti-oxidative parameters under MPs exposure.

Microalgal-bacterial biofilms for wastewater treatment: Operations, performances, mechanisms, and uncertainties.

Microalgal-bacterial biofilms have been increasingly considered of great potential in wastewater treatment due to the advantages of microalgal-bacterial synergistic pollutants removal/recovery, CO2 sequestration, and cost-effective biomass-water separation. However, such advantages may vary widely among different types of microalgal-bacterial biofilms, as the biofilms could be formed on different shapes and structures of attachment substratum, generating "false hope" for certain systems in large-scale wastewater treatment if the operating conditions and pollutants removal properties are evaluated based on the general term "microalgal-bacterial biofilm". This study, therefore, classified microalgal-bacterial biofilms into biofilms formed on 2D substratum, biofilms formed on 3D substratum, and biofilms formed without substratum (i.e. microalgal-bacterial granular sludge, MBGS). Biofilms formed on 2D substratum display higher microalgae fractions and nutrients removal efficiencies, while the adopted long hydraulic retention times were unacceptable for large-scale wastewater treatment. MBGS are featured with much lower microalgae fractions, most efficient pollutants removal, and acceptable retention times for realistic application, yet the feasibility of using natural sunlight should be further explored. 3D substratum systems display wide variations in operating conditions and pollutants removal properties because of diversified substratum shapes and structures. 2D and 3D substratum biofilms share more common in eukaryotic and prokaryotic microbial community structures, while MGBS biofilms are more enriched with microorganisms favoring EPS production, biofilm formation, and denitrification. The specific roles of stratified extracellular polymeric substances (EPS) in nutrients adsorption and condensation still require in-depth exploration. Nutrients removal uncertainties caused by microalgal-bacterial synergy decoupling under insufficient illumination, limited microbial community control, and possible greenhouse gas emission exacerbation arising from microalgal N2O generation were also indicated. This review is helpful for revealing the true potential of applying various microalgal-bacterial biofilms in large-scale wastewater treatment, and will provoke some insights on the challenges to the ideal state of synergistic pollutants reclamation and carbon neutrality via microalgal-bacterial interactions.

Rapid diagnosis and prognosis of de novo acute myeloid leukemia by serum metabonomic analysis.

Acute myeloid leukemia (AML) is a life-threatening hematological disease. Novel diagnostic and prognostic markers will be essential for new therapeutics and for significantly improving the disease prognosis. To characterize the metabolic features associated with AML and search for potential diagnostic and prognostic methods, here we analyzed the phenotypic characteristics of serum metabolite composition (metabonome) in a cohort of 183 patients with de novo acute myeloid leukemia together with 232 age- and gender-matched healthy controls using (1)H NMR spectroscopy in conjunction with multivariate data analysis. We observed significant serum metabonomic differences between AML patients and healthy controls and between AML patients with favorable and intermediate cytogenetic risks. Such differences were highlighted by systems differentiations in multiple metabolic pathways including glycolysis/gluconeogenesis, TCA cycle, biosynthesis of proteins and lipoproteins, and metabolism of fatty acids and cell membrane components, especially choline and its phosphorylated derivatives. This demonstrated the NMR-based metabonomics as a rapid and less invasive method for potential AML diagnosis and prognosis. The serum metabolic phenotypes observed here indicated that integration of metabonomics with other techniques will be useful for better understanding the biochemistry of pathogenesis and progression of leukemia.

π-Electron-Extended Triazine-Based Covalent Organic Framework as Photocatalyst for Organic Pollution Degradation and H2 Production from Water.

Herein, we report the efficient preparation of π-electron-extended triazine-based covalent organic framework (TFP-TPTPh COF) for photocatalysis and adsorption of the rhodamine B (RhB) dye molecule, as well as for photocatalytic hydrogen generation from water. The resultant TFP-TPTPh COF exhibited remarkable porosity, excellent crystallinity, high surface area of 724 m2 g-1, and massive thermal stability with a char yield of 63.41%. The TFP-TPTPh COF demonstrated an excellent removal efficiency of RhB from water in 60 min when used as an adsorbent, and its maximum adsorption capacity (Qm) of 480 mg g-1 is among the highest Qm values for porous polymers ever to be recorded. In addition, the TFP-TPTPh COF showed a remarkable photocatalytic degradation of RhB dye molecules with a reaction rate constant of 4.1 × 10-2 min-1 and an efficiency of 97.02% under ultraviolet-visible light irradiation. Furthermore, without additional co-catalysts, the TFP-TPTPh COF displayed an excellent photocatalytic capacity for reducing water to generate H2 with a hydrogen evolution rate (HER) of 2712 µmol g-1 h-1. This highly active COF-based photocatalyst appears to be a useful material for dye removal from water, as well as solar energy processing and conversion.

The long overlooked microalgal nitrous oxide emission: Characteristics, mechanisms, and influencing factors in microalgae-based wastewater treatment scenarios.

Microalgae-based wastewater treatment is particularly advantageous in simultaneous CO2 sequestration and nutrients recovery, and has received increasing recognition and attention in the global context of synergistic pollutants and carbon reduction. However, the fact that microalgae themselves can generate the potent greenhouse gas nitrous oxide (N2O) has been long overlooked, most previous research mainly regarded microalgae as labile organic carbon source or oxygenic approach that interfere bacterial nitrification-denitrification and the concomitant N2O production. This study, therefore, summarized the amount and rate of N2O emission in microalgae-based systems, interpreted in-depth the multiple pathways that lead to NO formation as the key precursor of N2O, and the pathways that transform NO into N2O. Reduction of nitrite could take place in either the cytoplasm or the mitochondria to form NO by a series of enzymes, while the NO could be enzymatically reduced to N2O at the chloroplasts or the mitochondria respectively under light and dark conditions. The influences of abiotic factors on microalgal N2O emission were analyzed, including nitrogen types and concentrations that directly affect the nitrogen transformation routes, illumination and oxygen conditions that regulate the enzymatic activities related to N2O generation, and other factors that indirectly interfere N2O emission via NO regulation. The uncertainty of microalgae-based N2O emission in wastewater treatment scenarios were emphasized, which would be particularly impacted by the complex competition between microalgae and ammonia oxidizing bacteria or nitrite oxidizing bacteria over ammonium or inorganic carbon source. Future studies should put more efforts in improving the compatibility of N2O emission results expressions, and adopting consistent NO detection methods for N2O emission prediction. This review will provide much valuable information on the characteristics and mechanisms of microalgal N2O emission, and arouse more attention to the non-negligible N2O emission that may impair overall greenhouse gas reduction efficiency in microalgae-based wastewater treatment systems.

Mechanistic insights into the allosteric inactivation mechanism of ZAP-70 induced by the hot spot W165C mutation.

Zeta chain-associated protein kinase 70 (ZAP-70) is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transduce downstream signals, and thus plays an important role in the adaptive immune system. The biphosphorylated immunotyrosine-based activation motifs (ITAM-Y2P) binds to the N-SH2 and C-SH2 domains of ZAP-70 to promote the activation of ZAP-70. The present study explores molecular mechanisms of allosteric inactivation of ZAP-70 induced by the hot spot W165C mutation through atomically detailed molecular dynamics simulation approaches. We report microsecond-length simulations of two states of the tandem SH2 domains of ZAP-70 in complex with the ITAM-Y2P motif, including the wild-type and W165C mutant. Extensive analysis of local flexibility and dynamical correlated motions show that W165C mutation changes coupled motions of protein domains and community networks. The binding affinities of the ITAM-Y2P motif to the wild-type and W165C mutant of ZAP-70 are predicted using binding free energy calculations. The results suggest that the driving force to decrease the binding affinity in the W165C mutant derives from the difference in the protein-protein electrostatic interactions. Moreover, the per-residue free energy decomposition unravels that the contributions from residues in the phosphorylated Tyr315 (pY315) binding site, in particular pY315 of ITAM-Y2P, and Arg43, Tyr240 of ZAP-70, are the key determinants for the loss of binding affinity. This study may insights into our understanding of the pathological mechanism of ZAP-70.Communicated by Ramaswamy H. Sarma.

Characteristics and management of vascular compromise after an organ transplantation surgery of the head and neck region: Analysis of 220 submandibular glands with autologous transplantation.

BACKGROUND: Microvascular submandibular gland transplantation (SMGT) for severe dry eye disease (DED) has rarely been reported in the literature. The aim of this study was to report a case series of SMGT with the special focus on monitoring and management of postoperative vascular compromise. METHODS: Using a retrospective single-cohort study design, the investigators enrolled a sample of DED patients undergoing SMGT in a Chinese university hospital during 1999 and 2021. The main outcomes were baseline and surgical data, post-operative manifestations, and surgical results. Descriptive, uni- and bivariate statistics were computed with the significant P < 0.05. RESULTS: During the study period, 220 DED patients (55.9% female) with a mean age of 32.66±14.47 years underwent SMGT. Vascular compromises occurred in 27 grafted glands (12.3%; 22 venous compromises and 5 arterial compromises) at a median of 27 h(range, 3.3 to 288 h) after surgery. Harden texture and swelling of the covering skin flap of the donor indicated venous compromises, while some specific sign was absent for arterial compromise. The accompanying vein of the facial artery (FAV) as a donor's vein was associated with less vascular compromise compared to the anterior facial vein (AFV). Timely reexploration was performed in 25 glands (92.6%), with a salvaged rate of 48%, and more venous compromises were salvaged compared to artery compromises (54.6% vs. 0%, P = 0.047). Temporary hypersecretion on postoperative 2-5 days was noticed in the grafted glands with no or salvaged vascular compromise (Schirmer's test, 35 mm/5 min and 37 mm/5 min, respectively, P = 0.749), while they were absent for the 15 surgically failed grands (Schirmer's test 0 mm/5 min, P<0.001). CONCLUSIONS: Vascular compromise appears to be a common complication of SMGT. Postoperative hypersecretion of the grafted glands may indicate good circulation, and the use of FAV as the donor's vein could help to decrease the risk of vascular compromise.

Growth-promoting effects of phytohormones on capillary-driven attached Chlorella sp. biofilm.

Using low strength wastewater for microalgae cultivation is challenged by slow growth and biomass harvesting issue in suspended systems, and growth-promoting effects of phytohormones at currently recommended dosages could neither obtain high enough biomass concentrations nor economic feasibility. This study aims to solve the issues of slow growth, biomass harvest, and phytohormone costs altogether by supplementing low dosage phytohormones in an improved capillary-driven attached cultivation device. The device displayed nutrients-condensing properties, and dosages of indole acetic acid (IAA), 6-benzylaminopurine (6-BA), and salicylic acid (SA) for highest microalgal growth were respectively 10-6 M, 10-6 M, and 10-7 M, being at least one order of magnitude lower than in suspended cultures. SA was most effective in growth-promoting (up to 7.0 g/m2 biomass density) and nutrients uptake (up to 98.6 % from the bulk environment), while IAA was most effective in antioxidative defenses. These results provided new insights in cost-effective and harvesting-convenient microalgae production.

Occurrence of antibiotics in waters, removal by microalgae-based systems, and their toxicological effects: A review.

Global antibiotics consumption has been on the rise, leading to increased antibiotics release into the environment, which threatens public health by selecting for antibiotic resistant bacteria and resistance genes, and may endanger the entire ecosystem by impairing primary production. Conventional bacteria-based treatment methods are only moderately effective in antibiotics removal, while abiotic approaches such as advanced oxidation and adsorption are costly and energy/chemical intensive, and may cause secondary pollution. Considered as a promising alternative, microalgae-based technology requires no extra chemical addition, and can realize tremendous CO2 mitigation accompanying growth related pollutants removal. Previous studies on microalgae-based antibiotics removal, however, focused more on the removal performances than on the removal mechanisms, and few studies have concerned the toxicity of antibiotics to microalgae during the treatment process. Yet understanding the removal mechanisms can be of great help for targeted microalgae-based antibiotics removal performances improvement. Moreover, most of the removal and toxicity studies were carried out using environment-irrelevant high concentrations of antibiotics, leading to reduced guidance for real-world situations. Integrating the two research fields can be helpful for both improving antibiotics removal and avoiding toxicological effects to primary producers by the residual pollutants. This study, therefore, aims to build a link connecting the occurrence of antibiotics in the aquatic environment, the removal of antibiotics by microalgae-based processes, and the toxicity of antibiotics to microalgae. Distribution of various categories of antibiotics in different water environments were summarized, together with the antibiotics removal mechanisms and performances in microalgae-based systems, and the toxicological mechanisms and toxicity of antibiotics to microalgae after either short-term or long-term exposure. Current research gaps and future prospects were also analyzed. The review could provide much valuable information to the related fields, and provoke interesting thoughts on integrating microalgae-based antibiotics removal research and toxicity research on the basis of environmentally relevant concentrations.