LSD1 in drug discovery: From biological function to clinical application.

Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.

Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function.

OBJECTIVES: Colitis is a global disease usually accompanied by intestinal epithelial damage and intestinal inflammation, and an increasing number of studies have found natural products to be highly effective in treating colitis. Anemoside B4 (AB4), an abundant saponin isolated from Pulsatilla chinensis (Bunge), which was found to have strong anti-inflammatory activity. However, the exact molecular mechanisms and direct targets of AB4 in the treatment of colitis remain to be discovered. METHODS: The anti-inflammatory activities of AB4 were verified in LPS-induced cell models and 2, 4, 6-trinitrobenzene sulfonic (TNBS) or dextran sulfate sodium (DSS)-induced colitis mice and rat models. The molecular target of AB4 was identified by affinity chromatography analysis using chemical probes derived from AB4. Experiments including proteomics, molecular docking, biotin pull-down, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to confirm the binding of AB4 to its molecular target. Overexpression of pyruvate carboxylase (PC) and PC agonist were used to study the effects of PC on the anti-inflammatory and metabolic regulation of AB4 in vitro and in vivo. RESULTS: AB4 not only significantly inhibited LPS-induced NF-κB activation and increased ROS levels in THP-1 cells, but also suppressed TNBS/DSS-induced colonic inflammation in mice and rats. The molecular target of AB4 was identified as PC, a key enzyme related to fatty acid, amino acid and tricarboxylic acid (TCA) cycle. We next demonstrated that AB4 specifically bound to the His879 site of PC and altered the protein's spatial conformation, thereby affecting the enzymatic activity of PC. LPS activated NF-κB pathway and increased PC activity, which caused metabolic reprogramming, while AB4 reversed this phenomenon by inhibiting the PC activity. In vivo studies showed that diisopropylamine dichloroacetate (DADA), a PC agonist, eliminated the therapeutic effects of AB4 by changing the metabolic rearrangement of intestinal tissues in colitis mice. CONCLUSION: We identified PC as a direct cellular target of AB4 in the modulation of inflammation, especially colitis. Moreover, PC/pyruvate metabolism/NF-κB is crucial for LPS-driven inflammation and oxidative stress. These findings shed more light on the possibilities of PC as a potential new target for treating colitis.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

NIS-Promoted Selective Amino-Diazidation and Amino-Iodoazidation of O-Homoallyl Benzimidates: Synthesis of Vicinal Diazido 1,3-Oxazines and Vicinal Iodoazido 1,3-Oxazines.

Amines, especially those with multi-nitrogen moieties, are widespread in natural products and biologically active compounds. Thus, the development of direct and efficient methods to introduce multiple nitrogen-containing fragments into compounds in one step is highly desirable yet challenging. Herein, we report an NIS-promoted selective amino-diazidation and amino-iodoazidation of O-homoallyl benzimidates with NaN3. By using this protocol, a variety of vicinal diazido-substituted 1,3-oxazines and vicinal iodoazido-substituted 1,3-oxazines were directly synthesized in a controllable manner. Preliminary mechanistic investigations revealed that the reaction operates through a NIS-promoted four-step cascade process. The developed method has the merits of metal-free, excellent functional group compatibility, simple operation, and mild conditions.

Magnetooptical Properties of Lanthanide(III) Metal-Organic Frameworks Based on an Iridium(III) Metalloligand.

Integrating magnetic and optical properties into a metal-organic framework (MOF) remains a great challenge. Herein, we have reasonably constructed two 3D magnetooptical MOFs by incorporating a [IrIII(ppy)2(bpy)]+-based fluorescent metalloligand and magnetic LnIII centers. The alternating arrangements of Δ- or Λ-[IrIII(ppy)2(bpy)]+ endow these MOFs with enhanced optical properties. Moreover, the use of DyIII leads to field-induced slow magnetic relaxation. This work provides an effective strategy for the preparation of magnetooptical bifunctional MOFs.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

A General Approach to Design Dual Ratiometric Fluorescent and Photoacoustic Probes for Quantitatively Visualizing Tumor Hypoxia Levels In†Vivo.

Herein, we describe an energy balance strategy between fluorescence and photoacoustic effects by sulfur substitution to transform existing hemicyanine dyes (Cy) into optimized NIRF/PA dual ratiometric scaffolds. Based on this optimized scaffold, we reported the first dual-ratio response of nitroreductase probe AS-Cy-NO2 , which allows quantitative visualization of tumor hypoxia in vivo. AS-Cy-NO2 , composed of a new NIRF/PA scaffold thioxanthene-hemicyanine (AS-Cy-1) and a 4-nitrobenzene moiety, showed a 10-fold ratiometric NIRF enhancement (I773 /I733 ) and 2.4-fold ratiometric PA enhancement (PA730 /PA670 ) upon activation by a biomarker (nitroreductase, NTR) associated with tumor hypoxia. Moreover, the dual ratiometric NIRF/PA imaging accurately quantified the hypoxia extent with high sensitivity and high imaging depth in xenograft breast cancer models. More importantly, the 3D maximal intensity projection (MIP) PA images of the probe can precisely differentiate the highly heterogeneous oxygen distribution in solid tumor. Thus, this study provides a promising NIRF/PA scaffold that may be generalized for the dual ratiometric imaging of other disease-relevant biomarkers.

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

An innovative adjustable prone positioning frame for treatment of severe kyphosis secondary to ankylosing spondylitis with two-level osteotomy.

PURPOSE: This study aims to introduce an innovative adjustable prone positioning frame (APPF) and explore its feasibility and safety for treatment of severe kyphosis secondary to ankylosing spondylitis (AS) with two-level osteotomy. METHODS: A retrospective, non-controlled study was conducted to illustrate the process where 13 patients diagnosed with severe kyphosis secondary to AS received operations on the APPF. Parameters of chin brow vertical angle (CBVA), global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL) and sagittal vertical axis (SVA) were measured. Positioning time, operation time, intraoperative blood loss ahd complications were also determined. The Scoliosis Research Society outcomes instrument (SRS-22) was applied for clinical assessment. RESULTS: All patients were placed on the APPF successfully with the positioning time of 2.92 ± 0.76 min, received operation with 457.00 ± 88.04 min and had blood loss of 2330.77 ± 1423.25 ml. Four cases experienced pain due to tensional skin of the abdomen and one case suffered cerebrospinal fluid leakage postoperatively, but these patients were all cured conservatively. No neurological complications were observed, although sagittal translation occurred in four patients. Significant improvements were detected in CBVA, GK, TLK, LL and SVA postoperatively (P < 0.05), but no significant difference was observed between postoperation and the final follow-up (P > 0.05). The SRS-22 scores at 2 years after operation were significantly higher than those before operation (P < 0.05). CONCLUSION: The innovative APPF provided great convenience to place patients with severe kyphosis secondary to AS in a prone position. Performing two-level osteotomy with the aid of APPF is safe, feasible and effective.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a "phototherapy-enzymatic" RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2 -hybridized OVA nanoanalogues (RuO2 @OVA NAs). The RuO2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

[Study on quality standard of fried Vaccariae Semen standard decoction].

According to the preparation principle of standard decoction of Chinese herbal medicines, fourteen batches of fried Vaccariae Semen decoction were prepared in this study and the quality research was carried out to establish a quality evaluation method for the standard decoction of fried Vaccariae Semen. The contents of vaccarin were determined, and its transfer rate from decoction piece to standard decoction was calculated. The extract rate and pH value were measured, and HPLC fingerprint method was established for analysis. The results of the 14 batches of samples revealed that the transfer rates of vaccarin were between 58.98%-93.94%; the extract rates were between 8.67%-17.83%, and the pH values were between 5.55-6.44. Moreover, 9 common chromatographic peaks were identified in fingerprints analysis. The similarities of the 14 batches of samples were analyzed and compared, and the results showed that the similarities were all higher than 0.96. In this study, the preparation process for fried Vaccariae Semen standard decoction was standard, with high similarities in fingerprint. A convenient and reliable method of comprehensive quality evaluation was established in this study, with a high precision, stability and repeatability, which can provide a reference for the quality control of fried Vaccariae Semen standard decoction, dispensing granule and related Chinese classical formulas(decoction).

Whole exome sequencing identified a novel mutation (p.Ala1884Pro) of ß-spectrin in a Chinese family with hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is an inherited disorder of erythrocyte. The typical feature of HS is the presence of spherical-shaped erythrocytes on the peripheral blood smear. According to previous studies, more than five candidate genes, such as ANK1, SPTB, SPTA1, SLC4A1 and EPB42 have been identified in HS patients. METHODS: In the present study, a Chinese HS family was investigated. The proband suffered from pathologic jaundice and splenomegaly. A blood test and peripheral blood smear experiment further confirmed the diagnosis of HS. We selected the proband to perform the whole exome sequencing. RESULTS: After data filtering and co-segregation analysis, we identified 12 mutations in affected members that were absent in healthy members. In consideration of the inheritance pattern, Online Mendelian Inheritance in Man clinical phenotypes, Toppgene function and American College of Medical Genetics classification, we considered the novel mutation (c.5650G > C/p.Ala1884Pro) of ß-spectrin (SPTB) to be the genetic lesion in this family. The novel mutation, resulting in a substitution of alanine by proline, may lead to transformation of the SPTB protein structure, which affects the binding between SPTB and ankyrin. CONCLUSIONS: The present study confirmed the hereditary red blood cell membrane disorders at a molecular level and expanded the spectrum of SPTB mutations. This may contribute to the clinical management and genetic counseling with respect to HS.

Antioxidant activity of phenylethanoid glycosides on glutamate-induced neurotoxicity.

Exposure of PC12 cells to 10 mM glutamate caused significant viability loss, cell apoptosis, decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA). In parallel, glutamate significantly increased the intracellular levels of ROS and intracellular calcium. However, pretreatment of the cells with acteoside and isoacteoside significantly suppressed glutamate-induced cellular events. Moreover, acteoside and isoacteoside reduced the glutamate-induced increase of caspase-3 activity and also ameliorated the glutamate-induced Bcl-2/Bax ratio reduction in PC12 cells. Furthermore, acteoside and isoacteoside significantly inhibited glutamate-induced DNA damage. In the mouse model, acteoside significantly attenuated cognitive deficits in the Y maze test and attenuated neuronal damage of the hippocampal CA1 regions induced by glutamate. These data indicated that acteoside and isoacteoside play neuroprotective effects through anti-oxidative stress, anti-apoptosis, and maintenance of steady intracellular calcium.

Solvent-Controlled Synthesis of Highly Luminescent Carbon Dots with a Wide Color Gamut and Narrowed Emission Peak Widths.

Carbon dots (CDs) have tremendous potential applications in bioimaging, biomedicine, and optoelectronics. By far, it is still difficult to produce photoluminescence (PL) tunable CDs with high quantum yield (QY) across the entire visible spectrum and narrow the emission peak widths of CDs close to those of typical quantum dots. In this work, a series of CDs with tunable emission from 443 to 745 nm, quantum yield within 13-54%, and narrowed full width at half maximum (FWHM) from 108 to 55 nm, are obtained by only adjusting the reaction solvents in a one-pot solvothermal route. The distinct optical features of these CDs are based on their differences in the particle size, and the content of graphitic nitrogen and oxygen-containing functional groups, which can be modulated by controlling the dehydration and carbonization processes during solvothermal reactions. Blue, green, yellow, red, and even pure white light emitting films (Commission Internationale de L'Eclairage (CIE)= 0.33, 0.33, QY = 39%) are prepared by dispersing one or three kinds of CDs into polyvinyl alcohol with appropriate ratios. The near-infrared emissive CDs are excellent fluorescent probes for both in vitro and in vivo bioimaging because of their high QY in water, long-term stability, and low cytotoxicity.

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China.

The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.

Highly Efficient Red-Emitting Carbon Dots with Gram-Scale Yield for Bioimaging.

Carbon dots (CDs) are a new class of photoluminescent (PL), biocompatible, environment-friendly, and low-cost carbon nanomaterials. Synthesis of highly efficient red-emitting carbon dots (R-CDs) on a gram scale is a great challenge at present, which heavily restricts the wide applications of CDs in the bioimaging field. Herein, R-CDs with a high quantum yield (QY) of 53% are produced on a gram scale by heating a formamide solution of citric acid and ethylenediamine. The as-prepared R-CDs have an average size of 4.1 nm and a nitrogen content of about 30%, with an excitation-independent emission at 627 nm. After detailed characterizations, such strong red fluorescence is ascribed to the contribution from the nitrogen- and oxygen-related surface states and the nitrogen-derived structures in the R-CD cores. Our R-CDs show good photostability and low cytotoxicity, and thus they are excellent red fluorescence probes for bioimaging both in vitro and in vivo.

Whole-Exome Sequencing Identifies Two Novel TTN Mutations in Chinese Families with Dilated Cardiomyopathy.

OBJECTIVES: Dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death. So far, only 127 mutations of Titin(TTN) have been reported in patients with different phenotypes such as isolated cardiomyopathies, purely skeletal muscle phenotypes or complex overlapping disorders of muscles. METHODS: We applied whole-exome sequencing (WES) to investigate cardiomyopathy patients and a cardiomyopathy-related gene-filtering strategy was used to analyze the disease-causing mutations. Sanger sequencing was applied to confirm the mutation cosegregation in the affected families. RESULTS: A nonsense mutation (c.12325C>T/p.R4109X) and a missense mutation (c.17755G>C/p.G5919R) of TTN were identified in 2 Chinese DCM families, respectively. Both mutations were cosegregated in all affected members of both families. The nonsense mutation is predicted to result in a truncated TTN protein and the missense mutation leads to a substitution of glycine by arginine. Both variants may cause the structure changes of titin protein. CONCLUSIONS: We employed WES to detect the mutations of DCM patients and identified 2 novel mutations. Our study expands the spectrum of TTN mutations and offers accurate genetic testing information for DCM patients who are still clinically negative.

Role of hippocampal ß-adrenergic and glucocorticoid receptors in the novelty-induced enhancement of fear extinction.

Fear extinction forms a new memory but does not erase the original fear memory. Exposure to novelty facilitates transfer of short-term extinction memory to long-lasting memory. However, the underlying cellular and molecular mechanisms are still unclear. Using a classical contextual fear-conditioning model, we investigated the effect of novelty on long-lasting extinction memory in rats. We found that exposure to a novel environment but not familiar environment 1 h before or after extinction enhanced extinction long-term memory (LTM) and reduced fear reinstatement. However, exploring novelty 6 h before or after extinction had no such effect. Infusion of the ß-adrenergic receptor (ßAR) inhibitor propranolol and glucocorticoid receptor (GR) inhibitor RU486 into the CA1 area of the dorsal hippocampus before novelty exposure blocked the effect of novelty on extinction memory. Propranolol prevented activation of the hippocampal PKA-CREB pathway, and RU486 prevented activation of the hippocampal extracellular signal-regulated kinase 1/2 (Erk1/2)-CREB pathway induced by novelty exposure. These results indicate that the hippocampal ßAR-PKA-CREB and GR-Erk1/2-CREB pathways mediate the extinction-enhancing effect of novelty exposure. Infusion of RU486 or the Erk1/2 inhibitor U0126, but not propranolol or the PKA inhibitor Rp-cAMPS, into the CA1 before extinction disrupted the formation of extinction LTM, suggesting that hippocampal GR and Erk1/2 but not ßAR or PKA play critical roles in this process. These results indicate that novelty promotes extinction memory via hippocampal ßAR- and GR-dependent pathways, and Erk1/2 may serve as a behavioral tag of extinction.

Carbon Dots/NiCo2 O4 Nanocomposites with Various Morphologies for High Performance Supercapacitors.

A series of carbon dots/NiCo2 O4 composites with various morphologies are prepared and tested for supercapacitors. These samples have good electrical conductivities and efficient ions transport paths, so they exhibit high specific capacitances, superior rate performances, and high cycling stabilities. The optimal composite for hybrid supercapacitor exhibits a high energy density up to 62.0 Wh kg-1 .

Defluviitalea phaphyphila sp. nov., a Novel Thermophilic Bacterium That Degrades Brown Algae.

Brown algae are one of the largest groups of oceanic primary producers for CO2 removal and carbon sinks for coastal regions. However, the mechanism for brown alga assimilation remains largely unknown in thermophilic microorganisms. In this work, a thermophilic alginolytic community was enriched from coastal sediment, from which an obligate anaerobic and thermophilic bacterial strain, designated Alg1, was isolated. Alg1 shared a 16S rRNA gene identity of 94.6% with Defluviitalea saccharophila LIND6LT2(T). Phenotypic, chemotaxonomic, and phylogenetic studies suggested strain Alg1 represented a novel species of the genus Defluviitalea, for which the name Defluviitalea phaphyphila sp. nov. is proposed. Alg1 exhibited an intriguing ability to convert carbohydrates of brown algae, including alginate, laminarin, and mannitol, to ethanol and acetic acid. Three gene clusters participating in this process were predicted to be in the genome, and candidate enzymes were successfully expressed, purified, and characterized. Six alginate lyases were demonstrated to synergistically deconstruct alginate into unsaturated monosaccharide, followed by one uronic acid reductase and two 2-keto-3-deoxy-d-gluconate (KDG) kinases to produce pyruvate. A nonclassical mannitol 1-phosphate dehydrogenase, catalyzing D-mannitol 1-phosphate to fructose 1-phosphate in the presence of NAD(+), and one laminarase also were disclosed. This work revealed that a thermophilic brown alga-decomposing system containing numerous novel thermophilic alginate lyases and a unique mannitol 1-phosphate dehydrogenase was adopted by the natural ethanologenic strain Alg1 during the process of evolution in hostile habitats.