Ferroelastically protected reversible orthorhombic to monoclinic-like phase transition in ZrO2 nanocrystals.

Robust ferroelectricity in nanoscale fluorite oxide-based thin films enables promising applications in silicon-compatible non-volatile memories and logic devices. However, the polar orthorhombic (O) phase of fluorite oxides is a metastable phase that is prone to transforming into the ground-state non-polar monoclinic (M) phase, leading to macroscopic ferroelectric degradation. Here we investigate the reversibility of the O-M phase transition in ZrO2 nanocrystals via in situ visualization of the martensitic transformation at the atomic scale. We reveal that the reversible shear deformation pathway from the O phase to the monoclinic-like (M') state, a compressive-strained M phase, is protected by 90° ferroelectric-ferroelastic switching. Nevertheless, as the M' state gradually accumulates localized strain, a critical tensile strain can pin the ferroelastic domain, resulting in an irreversible M'-M strain relaxation and the loss of ferroelectricity. These findings demonstrate the key role of ferroelastic switching in the reversibility of phase transition and also provide a tensile-strain threshold for stabilizing the metastable ferroelectric phase in fluorite oxide thin films.

"Matching Rule" for Generation, Modulation and Amplification of Circularly Polarized Luminescence.

ConspectusCircularly polarized luminescence (CPL) generated by chiral luminescent systems has sparked enormous attention in multidisciplinary field as it brings infinite potential for applications, such as 3D optical displays, biological probes, and chiroptical sensors. Satisfying both the conditions of chirality and luminescence (including fluorescence or phosphorescence) is a prerequisite for constructing CPL materials. In this regard, whether in organic, inorganic, or hybrid systems, chiral and luminescent components generally involve effective coupling through covalent or noncovalent bonds. For covalent interactions, such as the copolymerization of chiral and luminescent monomers, although covalent bonds provide high stability for the system, they inevitably involve tedious preparation procedures that connect chirality and luminescence together. For noncovalent bonds, take supramolecular assembly as an example, chiral elements and achiral light-emitting units are chiral transferred through intermolecular interactions, and their advantages include the diversity of luminescent and chiral building blocks, the stimuli responsiveness brought by noncovalent bonds, as well as the potential amplification of CPL signals by coassembly. However, the stability of the assembly system may be poor, and the assembly chiroptical performance and morphology are difficult to predict. Gratifyingly, matching rule that do not rely on covalent together with noncovalent interactions allows for the effortless construction, modulation, as well as amplification of CPL systems.In this Account, we overview different strategies based on matching rule, including fluorescence-selective absorption, circularly polarized reflection, and circularly polarized fluorescence energy transfer (CPF-ET). Examples of these strategies are illustrated with a focus on helical polymers in light of their appealing structures and wide uses. For instance, for fluorescence-selective absorption, chiral helical polymers can convert racemic fluorescence light into a circularly polarized one with specific handedness by simply overlapping the helical polymer's circular dichroism (CD) spectra with the luminophore's emission spectra. For circularly polarized reflection, employing the selective reflection of certain handedness's circularly polarized light, the high helical twisting power (HTP) of the helical polymer in the cholesteric liquid crystals (N*-LCs) gives the system high glum. Additionally, for CPF-ET, only the emission spectrum of the donor and the absorption (or excitation) spectrum of the achiral acceptor are required to overlap, and no covalent or noncovalent interactions between the two are required. An outlook for the CPL materials related to matching rule which will avail the optimization and extension of this intriguing approach concludes the Account. We hope that the Account will offer insightful inspiration for the flourishing progress of chiroptical systems and present exciting opportunities.

Structural basis of tolvaptan binding to the vasopressin V2 receptor.

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

Hot versus cold subduction initiation.

Initiation of a new subduction zone could act in two different ways, forming either a hot or cold incipient subduction channel with contrasting geological records.

High Internal Phase Emulsion for Constructing Chiral Helical Polymer-Based Circularly Polarized Luminescent Porous Materials.

Polymerized high internal phase emulsions (polyHIPEs) with circularly polarized luminescence (CPL), as an interesting class of porous materials, are of great significance for the development of CPL porous materials but have not been reported so far. Herein, we report the construction of polyHIPE-based CPL porous materials, taking advantage of an adsorption strategy. The pristine polyHIPEs constructed by chiral helical polymers, which acted as a chiral microenvironment, were fabricated by coordination polymerization of chiral acetylene monomers (R/S-SA) using HIPEs as templates. Achiral fluorescent small molecules were dispersed in the pores of the 3D porous organic chiral polymer matrix provided by polyHIPEs through the adsorption strategy, and CPL-active porous materials with blue, cyan, and green emissions were constructed using a fluorescence-selective absorption mechanism that does not rely on chirality transfer at the molecular level. The maximum luminescence dissymmetry factor (glum) value was -2.6 × 10-2. This work establishes a new and simple way for developing CPL porous materials.

Engineering a far-red fluorescent probe for rapid detection of Hg(II) ions in both cells and zebrafish.

Abnormal accumulation of mercury ions (Hg2+) in organisms can lead to severe central nervous system and other diseases. Therefore, the monitoring and detection of Hg2+ are of great significance for human health and environmental safety. Herein, we designed and synthesized a novel far-red to NIR emission fluorescent probe (Rho-Hg) based on rhodamine derivative as the fluorophore and thiospirolactone as the recognition site for turn-on detecting of Hg2+ in living cells and zebrafish. The probe Rho-Hg displayed superior sensitivity (detection limit = 17.5 nM), rapid response (<1 min), colorimetric change, high selectivity, and moderate pH stability. Leveraging this probe, we realized the real-time monitoring of Hg2+ in real samples, living cells and zebrafish. By fostering zebrafish embryos and larvae in Hg2+-containing nutrient solution, we noticed that Hg2+ was ingested into the zebrafish liver when zebrafish were grown up to 3 days old, and thus we successfully monitored the accumulation and changes of Hg2+ during zebrafish growth and development. Thus, the probe Rho-Hg could be a powerful tool for sensitive and real-time monitoring of Hg2+ in living systems.

Overexpression of microRNA-611 inhibits TGF-ß-induced epithelial-mesenchymal transition and migration in lung cancer cells through MAPKAP1.

Metastasis is a major cause of death in patients with lung cancer (LC). microRNA-611 (miR-611), a miRNA, has been little studied in cancer. Here, we aimed to further elucidate the roles of miR-611 in epithelial-mesenchymal transition (EMT) and migration induced by transforming growth factor-ß (TGF-ß) in LC cells and the possible underlying mechanisms. miR-611 and MAPKAP1 expression was first identified in LC tissues from metastatic and nonmetastatic patients, and their expression was associated with overall survival. Gain- and loss-of-function experiments were performed to verify the impacts of miR-611 and MAPKAP1 on pAKT expression, EMT, and migration in LC cells treated with TGF-ß. The interaction between miR-611 and MAPKAP1 was also determined with a luciferase reporter assay. In our study, miR-611 was expressed at low levels, and MAPKAP1 was highly expressed in LC tissues, which was associated with metastasis and short overall survival. Functionally, miR-611 inhibition or MAPKAP1 overexpression accelerated EMT and migration and upregulated pAKT in TGF-ß-treated A549 and H1299 cells; miR-611 overexpression or MAPKAP1 silencing exerted the opposite effects as miR-611 inhibition or MAPKAP1 overexpression. Mechanistically, miR-611 could target and downregulate MAPKAP1. MAPKAP1 expression was also negatively correlated with miR-611 expression in LC tissues. In addition, miR-611 overexpression reduced the EMT and migration of TGF-ß-treated A549 and H1299 cells by targeting MAPKAP1. In conclusion, miR-611 overexpression attenuated EMT and migration by targeting MAPKAP1 in TGF-ß-induced LC cells, indicating that miR-611 is a biological target for LC treatment.

Oxyimperatorin attenuates LPS-induced microglial activation in vitro and in vivo via suppressing NF-κB p65 signaling.

BACKGROUND: Microglia-mediated neuroinflammation is an important pathological feature in many neurological diseases; thus, suppressing microglial activation is considered a possible therapeutic strategy for reducing neuronal damage. Oxyimperatorin (OIMP) is a member of furanocoumarin, isolated from the medicinal herb Glehnia littoralis. However, it is unknown whether OIMP can suppress the neuroinflammation. PURPOSE: To investigate the neuroprotective activity of oxyimperatorin (OIMP) in LPS-induced neuroinflammation in vitro and in vivo models. METHODS: In vitro inflammation-related assays were performed with OIMP in LPS-induced BV-2 microglia. In addition, intraperitoneal injection of LPS-induced microglial activation in the mouse brain was used to validate the anti-neuroinflammatory activity of OIMP. RESULTS: OIMP was found to suppress LPS-induced neuroinflammation in vitro and in vivo. OIMP significantly attenuated LPS-induced the production of free radicals, inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines in BV-2 microglia without causing cytotoxicity. In addition, OIMP could reduce the M1 pro-inflammatory transition in LPS-stimulated BV-2 microglia. The mechanistic study revealed that OIMP inhibited LPS-induced NF-κB p65 phosphorylation and nuclear translocation. However, OIMP did not affect LPS-induced IκB phosphorylation and degradation. In addition, OIMP also was able to reduce LPS-induced microglial activation in mice brain. CONCLUSION: Our findings suggest that OIMP suppresses microglia activation and attenuates the production of pro-inflammatory mediators and cytokines via inhibition of NF-κB p65 signaling.

Preoperatively predicting vessels encapsulating tumor clusters in hepatocellular carcinoma: Machine learning model based on contrast-enhanced computed tomography.

BACKGROUND: Recently, vessels encapsulating tumor clusters (VETC) was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner, and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). AIM: To develop and validate a preoperative nomogram using contrast-enhanced computed tomography (CECT) to predict the presence of VETC+ in HCC. METHODS: We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers. Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase. Radiomics features, essential for identifying VETC+ HCC, were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set. The model's performance was validated on two separate test sets. Receiver operating characteristic (ROC) analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets. The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features. ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features, the radiomics features and the radiomics nomogram. RESULTS: The study included 190 individuals from two independent centers, with the majority being male (81%) and a median age of 57 years (interquartile range: 51-66). The area under the curve (AUC) for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825, 0.788, and 0.680 in the training set and the two test sets. A total of 13 features were selected to construct the Rad-score. The nomogram, combining clinical-radiological and combined radiomics features could accurately predict VETC+ in all three sets, with AUC values of 0.859, 0.848 and 0.757. Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models. CONCLUSION: This study demonstrates the potential utility of a CECT-based radiomics nomogram, incorporating clinical-radiological features and combined radiomics features, in the identification of VETC+ HCC.

Comprehensive genomic profiling of pulmonary spindle cell carcinoma using tissue and plasma samples: insights from a real-world cohort analysis.

Pulmonary spindle cell carcinoma (PSCC) is a rare and aggressive non-small cell lung cancer (NSCLC) subtype with a dismal prognosis. The molecular characteristics of PSCC are largely unknown due to its rarity, which limits the diagnosis and treatment of this historically poorly characterized malignancy. We present comprehensive genomic profiling results of baseline tumor samples from 22 patients histologically diagnosed with PSCC, representing the largest cohort to date. Somatic genetic variant detection was compared between paired plasma samples and primary tumors from 13 patients within our cohort. The associations among genomic features, treatment, and prognosis were also analyzed in representative patient cases. TP53 (54.5%), TERT (36.4%), CDKN2A (27.3%), and MET (22.7%) were most frequently mutated. Notably, 81.8% of patients had actionable targets in their baseline tumors, including MET (22.7%), ERBB2 (13.6%), EGFR (9.1%), KRAS (9.1%), ALK (9.1%), and ROS1 (4.5%). The median tumor mutation burden (TMB) for PSCC tumors was 5.5 mutations per megabase (muts/Mb). TMB-high tumors (>10 muts/Mb) exhibited a significantly higher mutation frequency in genes such as KRAS, ARID2, FOXL2, and LRP1B, as well as within the DNA mismatch repair pathway. The detection rates for single nucleotide variants and structural variants were comparable between matched tumor and plasma samples, with 48.6% of genetic variants being mutually identified in both sample types. Additionally, a patient with a high mutation load and positive PD-L1 expression demonstrated a 7-month survival benefit from chemoimmunotherapy. Furthermore, a patient with an ALK-rearranged tumor achieved a remarkable 3-year progression-free survival following crizotinib treatment. Overall, our findings deepen the understanding of the complex genomic landscape of PSCC, revealing actionable targets amenable to tailored treatment of this poorly characterized malignancy.

Highly Tribo-Positive Nylon-11 Film Fabricated by Multiscale Structural Regulation through a Roll-to-Roll Processing.

Triboelectric polymers have attracted extensive attention due to their great electron-accepting and electron-donating properties in contact electrification as well as their flexible and low-cost merits and have become promising electrode materials in triboelectric nanogenerators (TENGs). However, most research has exclusively focused on improving the electron capture capability of the triboelectric layer, neglecting to enhance the electron-donating capability, which leads to a low output performance of TENG and limits its practical application. In this study, we developed a method to fabricate highly tribo-positive Nylon-11 film through roll-to-roll processing. Paired with the poly(tetrafluoroethylene) triboelectric layer, the transferred charge density of contact-separation TENG based on Nylon-11 film prepared by this method reaches 291.1 µC/m2, which has been improved by 12.4% compared with the conventional compression molding sample. The novel fabricating method can regulate the surface functional groups to achieve higher surface potential and obtain a favorable pseudohexagonal crystal phase, leading to an increasing transferred charge density in triboelectrification. Additionally, it has been analyzed that higher chemical potential of materials can facilitate the transfer of electrons from the triboelectric polymer surface. This study provides a nonadditive, simple, and effective strategy to fabricate excellent tribo-positive material, which can significantly enhance the performance of TENG.

Progress in the Preparation and Application of Inulin-Based Hydrogels.

Inulin, a natural polysaccharide, has emerged as a promising precursor for the preparation of hydrogels due to its biocompatibility, biodegradability, and structural versatility. This review provides a comprehensive overview of the recent progress in the preparation, characterization, and diverse applications of inulin-based hydrogels. Different synthesis strategies, including physical methods (thermal induction and non-thermal induction), chemical methods (free-radical polymerization and chemical crosslinking), and enzymatic approaches, are discussed in detail. The unique properties of inulin-based hydrogels, such as stimuli-responsiveness, antibacterial activity, and their potential as fat replacers, are highlighted. Special emphasis is given to their promising applications in drug delivery systems, especially for colon-targeted delivery, due to the selective degradation of inulin via colonic microflora. The ability to incorporate both hydrophilic and hydrophobic drugs further expands their therapeutic potential. In addition, the applications of inulin-based hydrogels in responsive materials, the food industry, wound dressings, and tissue engineering are discussed. While significant progress has been achieved, challenges and prospects in optimizing synthesis, improving mechanical properties, and exploring new functionalities are discussed. Overall, this review highlights the remarkable properties of inulin-based hydrogels as a promising class of biomaterials with immense potential in the biomedical, pharmaceutical, and materials science fields.

Therapeutic efficacy of tranexamic acid on traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) demonstrates therapeutic efficacy in the management of traumatic brain injury (TBI). The objective of this systematic review and meta-analysis was to evaluate the safety and effectiveness of TXA in patients with TBI. METHODS: The databases, namely PubMed, Embase, Web of Science, and Cochrane Library databases, were systematically searched to retrieve randomized controlled trials (RCTs) investigating the efficacy of TXA for TBI from January 2000 to November 2023. RESULTS: The present meta-analysis incorporates ten RCTs. Compared to the placebo group, administration of TXA in patients with TBI resulted in a significant reduction in mortality (P = 0.05), hemorrhage growth (P = 0.03), and volume of hemorrhage growth (P = 0.003). However, no significant impact was observed on neurosurgery outcomes (P = 0.25), seizure occurrence (P = 0.78), or pulmonary embolism incidence (P = 0.52). CONCLUSION: The administration of TXA is significantly associated with reduced mortality and hemorrhage growth in patients suffering from TBI, while the need of neurosurgery, seizures, and incidence of pulmonary embolism remains comparable to that observed with placebo.

Recent Advances in Quaternary Ammonium Monomers for Dental Applications.

Resin-based dental materials have been one of the ideal choices among various materials in the treatment of dental caries. However, resin-based dental materials still have some drawbacks, such as the lack of inherent antibacterial activity. Extensive research has been conducted on the use of novel quaternary ammonium monomers (QAMs) to impart antibacterial activity to dental materials. This review provides a comprehensive overview of the recent advances in quaternary ammonium monomers (QAMs) for dental applications. The current progress and limitations of QAMs are discussed based on the evolution of their structures. The functional diversification and enhancement of QAMs are presented. QAMs have the potential to provide long-term antibacterial activity in dental resin composites, thereby prolonging their service life. However, there is a need to balance antibacterial performance with other material properties and the potential impact on the oral microbiome and general health. Finally, the necessity for further scientific progress in the development of novel quaternary ammonium monomers and the optimization of dental resin formulations is emphasized.

Operando monitoring of dendrite formation in lithium metal batteries via ultrasensitive tilted fiber Bragg grating sensors.

Lithium (Li) dendrite growth significantly deteriorates the performance and shortens the operation life of lithium metal batteries. Capturing the intricate dynamics of surface localized and rapid mass transport at the electrolyte-electrode interface of lithium metal is essential for the understanding of the dendrite growth process, and the evaluation of the solutions mitigating the dendrite growth issue. Here we demonstrate an approach based on an ultrasensitive tilted fiber Bragg grating (TFBG) sensor which is inserted close to the electrode surface in a working lithium metal battery, without disturbing its operation. Thanks to the superfine optical resonances of the TFBG, in situ and rapid monitoring of mass transport kinetics and lithium dendrite growth at the nanoscale interface of lithium anodes have been achieved. Reliable correlations between the performance of different natural/artificial solid electrolyte interphases (SEIs) and the time-resolved optical responses have been observed and quantified, enabling us to link the nanoscale ion and SEI behavior with the macroscopic battery performance. This new operando tool will provide additional capabilities for parametrization of the batteries' electrochemistry and help identify the optimal interphases of lithium metal batteries to enhance battery performance and its safety.

Analysis of delayed initial radioactive iodine therapy and clinical outcomes in papillary thyroid cancer: a two-center retrospective study.

BACKGROUND: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. METHODS: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n  = 317) and a delayed group (interval >90 days, n  = 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. RESULTS: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P  = 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n  = 332]; high-activity group: ≥5.5 GBq [ n  = 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P  < 0.05). CONCLUSION: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.

Recent Advances in the 3D Printing of Conductive Hydrogels for Sensor Applications: A Review.

Conductive hydrogels, known for their flexibility, biocompatibility, and conductivity, have found extensive applications in fields such as healthcare, environmental monitoring, and soft robotics. Recent advancements in 3D printing technologies have transformed the fabrication of conductive hydrogels, creating new opportunities for sensing applications. This review provides a comprehensive overview of the advancements in the fabrication and application of 3D-printed conductive hydrogel sensors. First, the basic principles and fabrication techniques of conductive hydrogels are briefly reviewed. We then explore various 3D printing methods for conductive hydrogels, discussing their respective strengths and limitations. The review also summarizes the applications of 3D-printed conductive hydrogel-based sensors. In addition, perspectives on 3D-printed conductive hydrogel sensors are highlighted. This review aims to equip researchers and engineers with insights into the current landscape of 3D-printed conductive hydrogel sensors and to inspire future innovations in this promising field.

Natural Chelating Agent-Treated Electron Transfer Layer for Friendly Environmental and Efficient Perovskite Solar Cells.

In perovskite solar cells (PSCs), the electron transfer layer (ETL) characteristics have significant effects on the photoelectric conversion efficiency (PCE) of the devices. Herein, a natural chelating agent polymer polyaspartic acid (PASP) is doped into the SnO2 precursor solution attributed to a strong interaction between PASP molecules and SnO2, which strengthens the interface contact and passivates the vacancy oxygen trap of the obtained SnO2 ETL, thus promoting the transfer of electrons. In addition, PASP can also regulate the growth of perovskite crystals, leading to an improved crystal quality of the perovskite films. Meanwhile, there is an excellent chelate anchoring of PASP to uncoordinated Pb2+, facilitating the reduction of trap defects at the interface, improving the stability of device, and suppressing the leakage of toxic Pb. Finally, the photovoltaic performance of the optimized device was greatly improved, and the PCE was increased from 21.22 to 23.49%, with outstanding environmental stability. This work provides an inexpensive and efficient treatment strategy that improves the performance and stability of friendly environmental PSCs.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma.

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

Integration of food raw materials, food microbiology, and food additives: systematic research and comprehensive insights into sweet sorghum juice, Clostridium tyrobutyricum TGL-A236 and bio-butyric acid.

Introduction: Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application. Methods: This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography-tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative real-time polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes. Results: The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained. Conclusion: This study not only includes a systematic process flow and in-depth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives.