Apolipoprotein B Secretion Assay from Primary Hepatocytes.

Apolipoprotein B (APOB) is the primary structural protein of atherogenic lipoproteins, which drive atherogenesis and thereby lead to deadly cardiovascular diseases (CVDs). Plasma levels of APOB-containing lipoproteins are tightly modulated by LDL receptor-mediated endocytic trafficking and cargo receptor-initiated exocytic route; the latter is much less well understood. This protocol aims to present an uncomplicated yet effective method for detecting APOB/lipoprotein secretion. We perform primary mouse hepatocyte isolation and culture coupled with well-established techniques such as immunoblotting for highly sensitive, specific, and semi-quantitative analysis of the lipoprotein secretion process. Its inherent simplicity facilitates ease of operation, rendering it a valuable tool widely utilized to explore the intricate landscape of cellular lipid metabolism and unravel the mechanistic complexities underlying lipoprotein-related diseases. Key features • A pipeline for the isolation and subsequent culture of mouse primary hepatocytes. • A procedure for tracking the secretion of APOB-containing lipoproteins. • A rapid and sensitive assay for detecting the APOB level based on immunoblotting.

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during midembryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these two paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two SAR1 paralogs, SAR1A and SAR1B. While these paralogs exhibit ~90% amino acid sequence identity, it is unknown whether they perform distinct or overlapping functions in vivo. We now report that genetic inactivation of Sar1a in mice results in lethality during mid-embryogenesis. We also confirm previous reports that complete deficiency of murine Sar1b results in perinatal lethality. In contrast, we demonstrate that deletion of Sar1b restricted to hepatocytes is compatible with survival, though resulting in hypocholesterolemia that can be rescued by adenovirus-mediated overexpression of either SAR1A or SAR1B. To further examine the in vivo function of these 2 paralogs, we genetically engineered mice with the Sar1a coding sequence replacing that of Sar1b at the endogenous Sar1b locus. Mice homozygous for this allele survive to adulthood and are phenotypically normal, demonstrating complete or near-complete overlap in function between the two SAR1 protein paralogs in mice. These data also suggest upregulation of SAR1A gene expression as a potential approach for the treatment of SAR1B deficiency (chylomicron retention disease) in humans.

Viruses in Marine Invertebrate Holobionts: Complex Interactions Between Phages and Bacterial Symbionts.

Marine invertebrates are ecologically and economically important and have formed holobionts by evolving symbiotic relationships with cellular and acellular microorganisms that reside in and on their tissues. In recent decades, significant focus on symbiotic cellular microorganisms has led to the discovery of various functions and a considerable expansion of our knowledge of holobiont functions. Despite this progress, our understanding of symbiotic acellular microorganisms remains insufficient, impeding our ability to achieve a comprehensive understanding of marine holobionts. In this review, we highlight the abundant viruses, with a particular emphasis on bacteriophages; provide an overview of their diversity, especially in extensively studied sponges and corals; and examine their potential life cycles. In addition, we discuss potential phage-holobiont interactions of various invertebrates, including participating in initial bacterial colonization, maintaining symbiotic relationships, and causing or exacerbating the diseases of marine invertebrates. Despite the importance of this subject, knowledge of how viruses contribute to marine invertebrate organisms remains limited. Advancements in technology and greater attention to viruses will enhance our understanding of marine invertebrate holobionts.

Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion.

OBJECTIVE: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. METHODS: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. RESULTS: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. CONCLUSIONS: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

Photocatalytic, modular difunctionalization of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer.

Ligand-to-metal charge transfer (LMCT) is a mechanistic strategy that provides a powerful tool to access diverse open-shell species using earth abundant elements and has seen tremendous growth in recent years. However, among many reaction manifolds driven by LMCT reactivity, a general and catalytic protocol for modular difunctionalization of alkenes remains unknown. Leveraging the synergistic cooperation of iron-catalyzed ligand-to-metal charge transfer and radical ligand transfer (RLT), here we report a photocatalytic, modular difunctionalization of alkenes using inexpensive iron salts catalytically to function as both radical initiator and terminator. Additionally, strategic use of a fluorine atom transfer reagent allows for general fluorochlorination of alkenes, providing the first example of interhalogen compound formation using earth abundant element photocatalysis. Broad scope, mild conditions and versatility in converting orthogonal nucleophiles (TMSN3 and NaCl) directly into corresponding open-shell radical species are demonstrated in this study, providing a robust means towards accessing vicinal diazides and homo-/hetero-dihalides motifs catalytically. These functionalities are important precursors/intermediates in medicinal and material chemistry. Preliminary mechanistic studies support the radical nature of these transformations, disclosing the tandem LMCT/RLT as a powerful reaction manifold in catalytic olefin difunctionalization.

Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples.

Carboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids. In general, our method renders a 5- to 2000-fold higher response in mass spectrometry along with improved chromatographic separation. With this method, we presented the near-single-cell analysis of carboxylic acid metabolites in 10 mouse egg cells before and after fertilization. Malate, fumarate, and ß-hydroxybutyrate were found to decrease after fertilization. We also monitored the isotope labeling kinetics of carboxylic acids inside adherent cells cultured in 96-well plates during drug treatment. Finally, we applied this method to plasma or serum samples (5 µL) collected from mice and humans under pathological and physiological conditions. The double click derivatization method paves a way toward single-cell metabolomics and bedside diagnostics.

Manganese regulation of COPII condensation controls circulating lipid homeostasis.

Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.

[Distribution Characteristics, Source Analysis and Potential Ecological Risk Assessment of Soil Heavy Metals in Typical River Source Areas of Northeastern Hunan Province].

Soil environmental quality in water source areas related to the residents' life, health and safety, has been the hotspot issues in science of ecological environment protection. A total of 87 surface soil samples were collected from typical river source areas in northeastern Hunan Province, using GIS technique and potential ecological risk assessment index to study the spatial distribution characteristics and Potential ecological risk of soil heavy metals (Cd, Pb, Cr, Hg and As), and the means of multivariate statistical analysis and positive definite matrix factor analysis models (PMF) were used to explain the possible sources and its contribution rates of heavy metals. The results show that:① The soil located in the typical river source area of northeastern Hunan Province was acidic, and the meant of ω(Cd), ω(Pb), ω(Cr), ω(Hg), and ω(As) in soil was 0.20, 41.07, 130.51, 0.29, and 11.63mg·kg-1, respectively. And except As, all of them had enrichment tendency. ② The comprehensive potential ecological risk of soil heavy metals was at a medium level, among which Cr, Pb and As were at a slight level of potential ecological risk, and Cd and Hg all reached a strong level of risk. ③ Cd and Pb of soil had significant homology, which were derived from agricultural activity, Cr and As of soil were affected by both domestic waste discharge and natural parent material, and Hg of soil was mainly derived from fossil combustion and transportation. ④ There were four pollution sources which included household waste discharge source, natural parent material source, Fossil burning and transportation sources, as well as sources of agricultural activities in typical river source area in northeastern Hunan Province, which contributed the rates of heavy metals were 21.36%, 35.92%, 19.30% and 23.42%, respectively, and the contribution rate of man-made sources was higher than that of natural sources. To sum up, this study has reference value for pollution prevention, ecological restoration and beautiful village construction in river source area of northeastern Hunan Province.

Photochemical iron-catalyzed decarboxylative azidation via the merger of ligand-to-metal charge transfer and radical ligand transfer catalysis.

Ligand-to-metal charge transfer (LMCT) using stoichiometric copper salts has recently been shown to permit decarboxylative C-N bond formation via an LMCT/radical polar crossover (RPC) mechanism; however, this method is unable to function catalytically and cannot successfully engage unactivated alkyl carboxylic acids, presenting challenges to the general applicability of this approach. Leveraging the concepts of ligand-to-metal charge transfer (LMCT) and radical-ligand-transfer (RLT), we herein report the first photochemical, iron-catalyzed direct decarboxylative azidation. Simply irradiating an inexpensive iron nitrate catalyst in the presence of azidotrimethylsilane allows for a diverse array of carboxylic acids to be converted to corresponding organic azides directly with broad functional group tolerance and mild conditions. Intriguingly, no additional external oxidant is required for this reaction to proceed, simplifying the reaction protocol. Finally, mechanistic studies are consistent with a radical mechanism and suggest that the nitrate counteranion serves as an internal oxidant for turnover of the iron catalyst.

Fabrication and characterization of novel thermoresponsive emulsion gels and oleogels stabilizied by assembling nanofibrous from dual natural triterpenoid saponins.

Novel thermoresponsive emulsion gels and oleogels were fabricated by assembling nanofibrous from natural triterpenoid Quillaja saponin (QS) and glycyrrhizic acid (GA). The viscoelasticity of QS-coated emulsion was observed to be remarkably improved by GA and thus obtain the advantages of excellent gelatinous, thermoresponsive and reversible manner due to the viscoelastic texture from GA nanofibrous as scaffolds in continuous phase. In the gelled emulsions, the phase transition of the GA fibrosis network structure upon heating and cooling was attributed to a thermal sensitivity, whereas interface-induced fibrosis assembly of amphiphilic QS endowed the formation of stable emulsion droplets. Then these emulsion gels were further used as an effective template to fabricate soft-solid oleogels with high oil content of 96%. These findings open up new opportunities for the use of all-natural and sustainable ingredients to develop smart soft materials for replace trans and saturated fats in food industry and other fields.

Towards the development of novel bicomponent phytosterol-based oleogels with natural phenolics.

Structuring liquid oils into edible oleogels from natural and abundant plant ingredients has great significance in fields ranging from foods to pharmaceuticals but has proven challenging. Herein, novel bicomponent phytosterol-based oleogels were developed with natural phenolics. Investigating diverse natural phenolics, cinnamic acid (CA) and ethyl ferulate (EF) successfully formed oleogels in combination with phytosterols (PS), where a synergistic effect on the oleogelation and crystallization was observed compared to the corresponding single component formulations. FTIR and UV-vis spectra showed that the gel network was primarily driven by hydrogen bonding and π-π stacking. Furthermore, oscillatory shear demonstrated oleogels featured higher elastic and network structure deformation at molar ratio of 5:5 and 3:7. Moreover, the bicomponent phytosterol-based oleogels displayed partially reversible shear deformation and a reversible solid-liquid transition. Such information was useful for engineering the functional properties of oleogel-based lipidic materials, providing significance for the application in foods, cosmetics and pharmaceuticals industries.

Enantioselective total syntheses of six natural and two proposed meroterpenoids from Psoralea corylifolia.

The first enantioselective total syntheses of six natural and two proposed meroterpenoids isolated from Psoralea corylifolia have been achieved in 7-9 steps from 2-methylcyclohexanone. The current synthetic approaches feature a high level of synthetic flexibility, stereodivergent fashion and short synthetic route, thereby providing a potential platform for the preparation of numerous this-type meroterpenoids and their pseudo-natural products.

[Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring].

OBJECTIVE: To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy. METHODS: From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria). RESULTS: All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05). CONCLUSION: The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

Misdiagnosis of scalp angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare malignant tumor. Owing to the lack of specific clinical manifestations of this disease, it is difficult to achieve early diagnosis and start early treatment. CASE SUMMARY: A 78-year-old male patient was admitted to the hospital because of a bump on his head that did not heal for 4 mo. The patient was diagnosed with a refractory head wound. The patient underwent neoplasm resection and skin grafting surgery in the Plastic Surgery. The neoplasm was sent for pathological examination during the operation. The final pathological results were confirmed scalp angiosarcoma. CONCLUSION: Our research suggests that pathological examination should be performed for refractory ulcers of the scalp, and physical factor therapy should be used with caution before the diagnosis is clear.

Microbiota-derived tryptophan metabolites indole-3-lactic acid is associated with intestinal ischemia/reperfusion injury via positive regulation of YAP and Nrf2.

BACKGROUND: Lactobacillus has been demonstrated to serve a protective role in intestinal injury. However, the relationship between Lactobacillus murinus (L. murinus)-derived tryptophan metabolites and intestinal ischemia/reperfusion (I/R) injury yet to be investigated. This study aimed to evaluate the role of L. murinus-derived tryptophan metabolites in intestinal I/R injury and the underlying molecular mechanism. METHODS: Liquid chromatograph mass spectrometry analysis was used to measure the fecal content of tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. Immunofluorescence, quantitative RT-PCR, Western blot, and ELISA were performed to explore the inflammation protective mechanism of tryptophan metabolites in WT and Nrf2-deficient mice undergoing intestinal I/R, hypoxia-reoxygenation (H/R) induced intestinal organoids. RESULTS: By comparing the fecal contents of three L. murinus-derived tryptophan metabolites in mice undergoing intestinal I/R injury and in patients undergoing cardiopulmonary bypass (CPB) surgery. We found that the high abundance of indole-3-lactic acid (ILA) in the preoperative feces was associated with better postoperative intestinal function, as evidenced by the correlation of fecal metabolites with postoperative gastrointestinal function, serum I-FABP and D-Lactate levels. Furthermore, ILA administration improved epithelial cell damage, accelerated the proliferation of intestinal stem cells, and alleviated the oxidative stress of epithelial cells. Mechanistically, ILA improved the expression of Yes Associated Protein (YAP) and Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) after intestinal I/R. The YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of ILA, both in vivo and in vitro. Additionally, we found that ILA failed to protect epithelial cells from oxidative stress in Nrf2 knockout mice under I/R injury. CONCLUSIONS: The content of tryptophan metabolite ILA in the preoperative feces of patients is negatively correlated with intestinal function damage under CPB surgery. Administration of ILA alleviates intestinal I/R injury via the regulation of YAP and Nrf2. This study revealed a novel therapeutic metabolite and promising candidate targets for intestinal I/R injury treatment.

Approach to evaluate the sensory quality deterioration of chicken seasoning using characteristic oxidation indicators.

Sensory quality deterioration of chicken seasoning was investigated using physicochemical properties, gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis to approach an evaluation of the chicken seasoning deterioration. It was found that both peroxide value (POV) and total oxidation value (TOTOX) increased with the chicken seasoning deterioration, suggesting a dominant of the lipid oxidation in the sensory quality deterioration of chicken seasoning. Moreover, a continuously decreasing linoleic acid and contradictory increasing in volatile aldehydes (specifically for hexanal) indicated as characteristic oxidation indicators to evaluate the sensory quality deterioration. PLSR results further elucidated that the evolution of aldehydes was highly correlated with sensory quality deterioration. These results suggest the POV, TOTOX and hexanal as valuable indicators and provide a novel approach to quality and rapidly evaluate the sensory quality deterioration of chicken seasoning.

[Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry].

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Edible HIPE-Gels and oleogels formed by synergistically combining natural triterpenoid saponin and citrus dietary fiber.

High-internal-phase emulsion gels (HIPE-Gels) and oleogels were successfully fabricated through synergistically combination of natural triterpenoid Quillaja saponin (QS) and citrus dietary fiber (CDF). The amphiphilic QS significantly lowered the oil-water interface tension; whereas CDF could form compact structure at the interface as well as in the bulk under a hydrogen-bonding interaction with saponin. The combination endowed the emulsion gels with enhanced performance, such as decreasing droplet size, strengthening gel network structure and better viscoelastic. At a very low QS of 0.045 %, stable HIPE-Gels can be produced with 0.3 % CDF, which mainly attributing to the highly viscoelastic fiber networks in continuous phase and thus actively trap the QS-coated emulsion droplets. Consequently, the robust HIPE-Gels were applied as soft template to fabricate oleogels with controlled by QS and CDF loading. These findings proved an effective strategy towards structuring edible liquid oil into healthy gels for alternating saturated and trans fats in foods.

Efficient isopropanol-butanol-ethanol (IBE) fermentation by a gene-modified solventogenic Clostridium species under the co-utilization of Fe(III) and butyrate.

To elevate the efficiency of acetone-butanol-ethanol (ABE) fermentation by the wild-type strain WK, an optimal co-utilization system (20 mM Fe3+ and 5 g/L butyrate) was established to bring about a 22.22% increment in the yield of ABE mixtures with a significantly enhanced productivity (0.32 g/L/h). With the heterologous introduction of the secondary alcohol dehydrogenase encoded gene (adh), more than 95% of acetone was eliminated to convert 4.5 g/L isopropanol with corresponding increased butanol and ethanol production by 21.08% and 65.45% in the modified strain WK::adh. Under the optimal condition, strain WK::adh was capable of producing a total of 25.46 g/L IBE biosolvents with an enhanced productivity of 0.35 g/L/h by 45.83% over the original conditions. This work for the first time successfully established a synergetic system of co-utilizing Fe(III) and butyrate to demonstrate a feasible and efficient manner for generating the value-added biofuels through the metabolically engineered solventogenic clostridial strain.