Current trends and possibilities of typical microbial protein production approaches: a review.

Global population growth and demographic restructuring are driving the food and agriculture sectors to provide greater quantities and varieties of food, of which protein resources are particularly important. Traditional animal-source proteins are becoming increasingly difficult to meet the demand of the current consumer market, and the search for alternative protein sources is urgent. Microbial proteins are biomass obtained from nonpathogenic single-celled organisms, such as bacteria, fungi, and microalgae. They contain large amounts of proteins and essential amino acids as well as a variety of other nutritive substances, which are considered to be promising sustainable alternatives to traditional proteins. In this review, typical approaches to microbial protein synthesis processes were highlighted and the characteristics and applications of different types of microbial proteins were described. Bacteria, fungi, and microalgae can be individually or co-cultured to obtain protein-rich biomass using starch-based raw materials, organic wastes, and one-carbon compounds as fermentation substrates. Microbial proteins have been gradually used in practical applications as foods, nutritional supplements, flavor modifiers, and animal feeds. However, further development and application of microbial proteins require more advanced biotechnological support, screening of good strains, and safety considerations. This review contributes to accelerating the practical application of microbial proteins as a promising alternative protein resource and provides a sustainable solution to the food crisis facing the world.

Neoadjuvant savolitinib targeted therapy for stage IIIB-N3 lung adenocarcinoma harboring mesenchymal-epithelial transition exon 14 skipping mutation: a case report and literature review.

Savolitinib is a selective inhibitor that specifically targets the phosphorylation of mesenchymal-epithelial transition (MET) kinase. It has demonstrated significant inhibitory effects on the proliferation of tumor cells with METex14 skipping mutation, making it a promising treatment option. While it is the first approved small-molecule inhibitor specifically targeting MET kinase in China, there is limited information about its efficacy as neoadjuvant therapy for patients with supraclavicular lymph node metastasis (N3). In this case report, we presented the successful outcome of a 48-year-old male patient who was diagnosed with stage IIIB (T2bN3M0) lung adenocarcinoma originating from the left upper lobe. The patient exhibited the METex14 skipping alteration. Following two months of neoadjuvant savolitinib treatment, the patient achieved partial remission, with a significant reduction in the size of the primary tumor and metastatic lymph nodes. Postoperative pathological confirmation revealed a pathological complete response, and subsequent imaging examinations, including computed tomography scan and circulating tumor DNA-based molecular residual disease detection, showed no sign of recurrence at 7 months after surgery. Based on this case, neoadjuvant and adjuvant savolitinib therapy may be considered as a favorable alternative to chemotherapy for marginally resectable nonsmall cell lung cancer patients with METex14 skipping mutation.

Lighting up endogenous H2O2 in the tumor microenvironment using a dual-mode nanoprobe for long afterglow and MR bioimaging.

Persistent luminescent nanoparticles (PLNPs) are excellent luminescent materials, and near-infrared PLNPs are efficiently applied for biosensing and bioimaging due to their advantages of no excitation, excellent light stability and long afterglow. However, due to interference from the complex environment within organisms, single-mode imaging methods often face limitations in selectivity, sensitivity, and accuracy. Therefore, it is desirable to construct a dual-mode imaging probe strategy with higher specificity and sensitivity for bioimaging. Magnetic resonance imaging (MRI) has been widely used in the field of bioimaging due to its advantages of high resolution, non-radiation and non-invasiveness. Here, by combining near-infrared PLNPs and manganese dioxide (MnO2) nanosheets, a sensitive and convenient dual-mode "turn on" bioimaging nanoprobe ZGC@MnO2 has been developed for long afterglow imaging and MRI of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment (TME). The monitoring of H2O2 has garnered significant attention due to its crucial role in human pathologies. For the dual-mode "turn on" bioimaging nanoprobe, the near-infrared PLNPs of quasi-spherical ZnGa2O4:Cr (ZGC) nanoparticles were synthesized as luminophores, and MnO2 nanosheets were utilized as a fluorescence quencher, carrier and H2O2 recognizer. H2O2 in the TME could reduce MnO2 nanosheets to Mn2+ for MRI, and ZGC nanoparticles were released for long afterglow imaging. Finally, the ZGC@MnO2 nanoprobe exhibited a rapid response, an excellent signal-to-noise ratio and a limit of detection of 3.67 nM for endogenous H2O2 in the TME. This dual-mode approach enhances the detection sensitivity for endogenous H2O2, thereby facilitating the research of endogenous H2O2-associated diseases and clinical diagnostics.

Opposite evolution of pathogenicity driven by in vivo wzc and wcaJ mutations in ST11-KL64 carbapenem-resistant Klebsiella pneumoniae.

AIMS: To investigate the in vivo evolution of the mucoid-phenotype of ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from the same patients and gain insights into diverse evolution and biology of these strains. METHODS: Whole genome sequencing and bioinformatic analysis were used to determine the mutation involved in the mucoid phenotype of ST11-KL64 CRKP. Gene knockout, bacterial morphology and capsular polysaccharides (CPS) extraction were used to verify the role of wzc and wcaJ in the mucoid phenotypes. Antimicrobial susceptibility, growth assay, biofilm formation, host cell adhesion and virulence assay were used to investigate the pleiotropic role of CPS changes in ST11-KL64 CRKP strains. RESULTS: Mutation of wzc S682N led to hypermucoid phenotype, which had negative impact on bacterial fitness and resulted in reduced biofilm formation and epithelial cell adhesion; while enhanced resistance to macrophage phagocytosis and virulence. Mutations of wcaJ gene led to non-mucoid phenotype with increased biofilm formation and epithelial cell adhesion, but reduced resistance of macrophage phagocytosis and virulence. Using virulence gene knockout, we demonstrated that CPS, rather than the pLVPK-like virulence plasmid, has a greater effect on mucoid phenotypic changes. CPS could be used as a surrogate marker of virulence in ST11-KL64 CRKP strains. CONCLUSIONS: ST11-KL64 CRKP strains sacrifice certain advantages to develop pathogenicity by changing CPS with two opposite in vivo evolution strategies.

Solar-Powered Interfacial Evaporation and Deicing Based on a 3D-Printed Multiscale Hierarchical Design.

Solar-powered interfacial heating has emerged as a sustainable technology for hybrid applications with minimal carbon footprints. Aerogels, hydrogels, and sponges/foams are the main building blocks for state-of-the-art photothermal materials. However, these conventional three-dimensional (3D) structures and related fabrication technologies intrinsically fail to maximize important performance-enhancing strategies and this technology still faces several performance roadblocks. Herein, monolithic, self-standing, and durable aerogel matrices are developed based on composite photothermal inks and ink-extrusion 3D printing, delivering all-in-one interfacial steam generators (SGs). Rapid prototyping of multiscale hierarchical structures synergistically reduce the energy demand for evaporation, expand actual evaporation areas, generate massive environmental energy input, and improve mass flows. Under 1 sun, high water evaporation rates of 3.74 kg m-2 h-1 in calm air and 25.3 kg m-2 h-1 at a gentle breeze of 2 m s-1 are achieved, ranking among the best-performing solar-powered interfacial SGs. 3D-printed microchannels and hydrophobic modification deliver an icephobic surface of the aerogels, leading to self-propelled and rapid removal of ice droplets. This work shines light on rational fabrication of hierarchical photothermal materials, not merely breaking through the constraints of solar-powered interfacial evaporation and clean water production, but also discovering new functions for photothermal interfacial deicing.

An insight into the health beneficial of probiotics dairy products: a critical review.

Probiotic dairy products satisfy people's pursuit of health, and are widely favored because of their easy absorption, high nutritional value, and various health benefits. However, its effectiveness and safety are still controversial. This proposal aims to analyze the effect of probiotics on the quality characteristics of dairy products, clarify a series of physiological functions of probiotic dairy products and critically evaluate the effectiveness and safety of probiotic dairy products. Also, dairy products containing inactivated microorganisms were compared with probiotic products. The addition of probiotics enables dairy products to obtain unique quality characteristics, and probiotic dairy products have better health-promoting effects. This review will promote the further development of probiotic dairy products, provide directions for the research and development of probiotic-related products, and help guide the general public to choose and purchase probiotic fermentation products.

Resource recovery and valorization of food wastewater for sustainable development: An overview of current approaches.

The food processing industry is one of the world's largest consumers of potable water. Agri-food wastewater systems consume about 70% of the world's fresh water and cause at least 80% of deforestation. Food wastewater is characterized by complex composition, a wide range of pollutants, and fluctuating water quality, which can cause huge environmental pollution problems if discharged directly. In recent years, food wastewater has attracted considerable attention as it is considered to have great prospects for resource recovery and reuse due to its rich residues of nutrients and low levels of harmful substances. This review explored and compared the sources and characteristics of different types of food wastewater and methods of wastewater treatment. Particular attention was paid to the different methods of resource recovery and reuse of food wastewater. The diversity of raw materials in the food industry leads to different compositional characteristics of wastewater, which determine the choice and efficiency of wastewater treatment methods. Physicochemical methods, and biological methods alone or in combination have been used for the efficient treatment of food wastewater. Current approaches for recycling and reuse of food wastewater include culture substrates, agricultural irrigation, and bio-organic fertilizers, recovery of high-value products such as proteins, lipids, biopolymers, and bioenergy to alleviate the energy crisis. Food wastewater is a promising substrate for resource recovery and reuse, and its valorization meets the current international policy requirements regarding food waste and environment protection, follows the development trend of the food industry, and is also conducive to energy conservation, emission reduction, and economic development. However, more innovative biotechnologies are necessary to advance the effectiveness of food wastewater treatment and the extent of resource recovery and valorization.

Toward improvements for enhancement the productivity and color value of Monascus pigments: a critical review with recent updates.

Monascus pigments are a kind of high-quality natural edible pigments fermented by Monascus filamentous fungi, which have been widely used in food, cosmetics, medicine, textiles, dyes and chemical industries as active functional ingredients. Moreover, Monascus pigments have a good application prospect because of a variety of biological functions such as antibacterial, antioxidation, anti-inflammatory, regulating cholesterol, and anti-cancer. However, the low productivity and color value of pigments restrict their development and application. In this review, we introduced the categories, structures, biosynthesis and functions of Monascus pigments, and summarized the current methods for improving the productivity and color value of pigments, including screening and mutagenesis of strains, optimization of fermentation conditions, immobilized fermentation, mixed fermentation, additives, gene knockout and overexpression technologies, which will help to develop the foundation for the industrial production of Monascus pigments.

Virgin coconut oil: A comprehensive review of antioxidant activity and mechanisms contributed by phenolic compounds.

Virgin coconut oil (VCO) is obtained by processing mature coconut cores with mechanical or natural methods. In recent years, VCO has been widely used in the food, pharmaceutical, and cosmetic industries because of its excellent functional activities. VCO has biological functions such as antioxidant, anti-inflammatory, antibacterial, and antiviral, and also has potential therapeutic effects on many chronic degenerative diseases. Among these functions, the antioxidant is the most basic and important function, which is mainly determined by phenolic compounds and medium-chain fatty acids (MCFAs). This review aims to elucidate the antioxidant functions of each phenolic compound in VCO, and discuss the antioxidant mechanisms of VCO in terms of the role of phenolic compounds with fat, intestinal microorganisms, and various organs. Besides, the composition of VCO and its application in various industries are summarized, and the biological functions of VCO are generalized, which should lay a foundation for further research on the antioxidant activity of VCO and provide a theoretical basis for the development of food additives with antioxidant activity.

Probiotic potentials of the silkworm gut symbiont Enterococcus casseliflavus ECB140, a promising L-tryptophan producer living inside the host.

AIMS: L-tryptophan is an essential aromatic amino acid for the growth and development of animals. Studies about enteric L-tryptophan-producing bacteria are scarce. In this report, we characterized the probiotic potential of Enterococcus casseliflavus ECB140, focusing on its L-tryptophan production abilities. METHODS AND RESULTS: ECB140 strain was isolated from the silkworm gut and can survive under strong alkaline environmental conditions. Bacterial colonization traits (motility and biofilm) were examined and showed that only ECB140 produced flagellum and strong biofilms compared with other Enterococcus strains. Comparative genome sequence analyses showed that only ECB140 possessed a complete route for L-tryptophan synthesis among all 15 strains. High-performance liquid chromatography and qRT-PCR confirmed the capability of ECB140 to produce L-tryptophan. Besides, the genome also contains the biosynthesis pathways of several other essential amino acids, such as phenylalanine, threonine, valine, leucine, isoleucine and lysine. These results indicate that ECB140 has the ability to survive passage through the gut and could act as a candidate probiotic. CONCLUSIONS: The study describes a novel, natural silkworm gut symbiont capable of producing L-tryptophan. Enterococcus casseliflavus ECB140 physical and genomic attributes offer possibilities for its colonization and provide L-tryptophan for lepidopteran insects.

Ttc39c is a potential target for the treatment of lung cancer.

BACKGROUND: The novel TTC gene, tetratricopeptide repeat domain 39 C (Ttc39c), mainly mediates the interaction between proteins. It is involved in the progression of various tumors. In this study, we determined the effect of Ttc39c on lung adenocarcinoma and found that it might be used as a potential intervention target. METHODS: We performed a difference analysis of Ttc39c samples from the TCGA database. Transwell experiments were conducted to determine the ability of cell metastasis. Celigo and MTT assays were performed to determine the effect of Ttc39c gene subtraction on cell proliferation. FACS was performed to determine the effect of Ttc39c gene subtraction on apoptosis. Clone-formation experiments were conducted to determine the effect of Ttc39c gene subtraction on cloning ability. Transcriptomics, proteomics, and metabolomics were used to elucidate the enrichment pathway of the Ttc39c gene in the progression of lung adenocarcinoma. RESULTS: The expression of Ttc39c increased significantly in lung adenocarcinoma. The proliferation, metastasis, and cloning ability of human lung cancer cells were inhibited, while the apoptosis of cells increased significantly after the depletion of Ttc39c. Our results based on the transcriptomics, proteomics, and metabolomics analyses indicated that Ttc39c might be involved in the progression of lung adenocarcinoma (LUAD) mainly through the metabolic pathway and the p53 pathway. CONCLUSION: To summarize, Ttc39c strongly regulates the proliferation and metastasis of lung adenocarcinoma cells. The main pathways involved in Ttc39c in lung adenocarcinoma include the energy metabolism and p53 pathways.

Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer.

INTRODUCTION: Pulmonary cancer is a kind of deeply invasive tumour which is difficult to treat, and its mortality rate is high. Previous research has shown that activation of complement could contribute to the progression of non-small-cell lung cancer (SCLC). However, little research has been done on SCLC. METHODS: Complement factor H (CFH), complements C3 as well as C4 were measured in patients, and the prognostic impact of different parameters was assessed by log-rank function analysis and Cox multifactor models. Besides, we constructed a predictive model based on complement fractions and validated the accuracy of the model. RESULTS: Among these 242 patients, 200 (82.6%) died. The median survival time was 18.3 months. We found by multifactorial analysis that high levels of CFH decreased the risk of death (HR 0.23, 95% CI 0.10 to 0.57, p<0.001), while elevated complement C4 displayed poor prognosis (HR 2.28, 95% CI 1.66 to 3.13, p<0.001). We screened variables by Cox models and constructed CFH-based prediction models to plot a nomogram by internal validation. The nomogram showed excellent accuracy in assessing the probability of death, yielding an adjusted C-statistics of 0.905. CONCLUSIONS: CFH can be recognised as a biomarker to predict the risk of death in SCLC. The prediction model established based on CFH, C3 and C4 levels has good accuracy in patients' prognostic assessment.

CRISPR/Cas9-Mediated Genome Editing for Pseudomonas fulva, a Novel Pseudomonas Species with Clinical, Animal, and Plant-Associated Isolates.

As one of the most widespread groups of Gram-negative bacteria, Pseudomonas bacteria are prevalent in almost all natural environments, where they have developed intimate associations with plants and animals. Pseudomonas fulva is a novel species of Pseudomonas with clinical, animal, and plant-associated isolates, closely related to human and animal health, plant growth, and bioremediation. Although genetic manipulations have been proven as powerful tools for understanding bacterial biological and biochemical characteristics and the evolutionary origins, native isolates are often difficult to genetically manipulate, thereby making it a time-consuming and laborious endeavor. Here, by using the CRISPR-Cas system, a versatile gene-editing tool with a two-plasmid strategy was developed for a native P. fulva strain isolated from the model organism silkworm (Bombyx mori) gut. We harmonized and detailed the experimental setup and clarified the optimal conditions for bacteria transformation, competent cell preparation, and higher editing efficiency. Furthermore, we provided some case studies, testing and validating this approach. An antibiotic-related gene, oqxB, was knocked out, resulting in the slow growth of the P. fulva deletion mutant in LB containing chloramphenicol. Fusion constructs with knocked-in gfp exhibited intense fluorescence. Altogether, the successful construction and application of new genetic editing approaches gave us more powerful tools to investigate the functionalities of the novel Pseudomonas species.

Acquisition of a genomic resistance island (AbGRI5) from global clone 2 through homologous recombination in a clinical Acinetobacter baumannii isolate.

OBJECTIVES: To reconstruct the evolutionary history of the clinical Acinetobacter baumannii XH1056, which lacks the Oxford scheme allele gdhB. METHODS: Susceptibility testing was performed using broth microdilution and agar dilution. The whole-genome sequence of XH1056 was determined using the Illumina and Oxford Nanopore platforms. MLST was performed using the Pasteur scheme and the Oxford scheme. Antibiotic resistance genes were identified using ABRicate. RESULTS: XH1056 was resistant to all antibiotics tested, apart from colistin, tigecycline and eravacycline. MLST using the Pasteur scheme assigned XH1056 to ST256. However, XH1056 could not be typed with the Oxford MLST scheme as gdhB is not present. Comparative analyses revealed that XH1056 contains a 52 933 bp region acquired from a global clone 2 (GC2) isolate, but is otherwise closely related to the ST23 A. baumannii XH858. The acquired region in XH1056 also contains a 34 932 bp resistance island that resembles AbGRI3 and contains the armA, msrE-mphE, sul1, blaPER-1, aadA1, cmlA1, aadA2, blaCARB-2 and ere(B) resistance genes. Comparison of the XH1056 chromosome to that of GC2 isolate XH859 revealed that the island in XH1056 is in the same chromosomal region as that in XH859. As this island is not in the standard AbGRI3 position, it was named AbGRI5. CONCLUSIONS: XH1056 is a hybrid isolate generated by the acquisition of a chromosomal segment from a GC2 isolate that contains a resistance island in a new location-AbGRI5. As well as generating ST256, it appears likely that a single recombination event is also responsible for the acquisition of AbGRI5 and its associated antibiotic resistance genes.

Environmental Assessment of SARS-CoV-2 for Internal Quality Management in a Clinical Laboratory.

BACKGROUND: As an emerging infectious disease, coronavirus disease 2019 (COVID-19) exhibits occult infection, which might cause difficulties in controlling disease spread. The possibility of aerosol transmission in a relatively closed environment contributes to the high infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hospitals. This study presents an environmental surveillance system for SARS-CoV-2 that is suitable for a clinical laboratory and may also lead to further assessment of infection prevention programs in different departments in hospitals. METHODS: The study was performed in a SARS-CoV-2 RNA laboratory involved in the diagnosis of COVID-19 in China. Reverse transcription-polymerase chain reaction (RT-PCR) assays were used to detect viral pathogens. Standard operating procedures (SOPs) for monitoring infectious pathogens were developed in this study. RESULTS: In total, more than 180 air and surface samples were tested for SARS-CoV-2 to determine whether the virus was present at the airborne and particle level. The employed molecular method effectively identified environmental contamination. CONCLUSIONS: Our study suggests that regular environmental surveillance is critical in a clinical PCR laboratory. The presented strategy could also be used for monitoring and surveillance in negative pressure wards and clinics in hospitals to prevent hospital-acquired infections.

Creating tidal flow via siphon for better pollutants removal in a microbial fuel cell-constructed wetland.

Oxygen is the electron acceptor in cathode chamber of microbial fuel cell-constructed wetland system (MFC-CW). The objective of the study lies in creating a "tidal flow" (TF) in cathode chamber via a siphon to enhance the oxygen diffusion, thus promoting the system performance. A laboratory scale MFC-CW with a siphon driven TF recirculation was proposed and designed. It allows the variable water level being created in four operational modes. The results demonstrated the significance of the siphon which was reflected by the attractive wastewater treatment performance. Compared with the tested four operational modes under the same hydraulic condition, the highest total nitrogen removal efficiency of 96.32% and COD removal efficiency of 92.37% were achieved, respectively, in 1st full siphon recirculation mode (FSR) and 2nd FSR operation mode. Indeed, the water level variation range played an important role in pollutants removal performance. Reduced water level variation of the TF in cathode chamber hindered excessive oxygen diffusion into MFC-CW and thus adversely affected the system performance. It is clear that the siphon is a wiser input to bring about the better treatment performance, but it is believed that the enhanced microbial activities behind the oxygen promotion is the driven force to exhibiting a better performance in the MFC-CW system.

The distribution of mutations and hotspots in transcription regulators of resistance-nodulation-cell division efflux pumps in tigecycline non-susceptible Acinetobacter baumannii in China.

OBJECTIVE: Acinetobacter baumannii has emerged as a problematic hospital pathogen and tigecycline is among the few remaining antibiotics retaining activity against multidrug-resistant A. baumannii. This study was aimed to elucidate the tigecycline resistance mechanisms in 28 unique clinical A. baumannii strains from nine provinces in China. METHODS: Whole genome sequences were obtained via Illumina HiSeq sequencing and regulatory genes of efflux pumps were analyzed. Minimal inhibitory concentrations (MICs) were determined by agar/microbroth dilution according to the guidelines recommended by Clinical and Laboratory Standards Institute (CLSI). Tigecycline susceptibility data was interpreted using breakpoints for Enterobacterales recommended by EUCAST v8.1. RESULTS: The majority of isolates belonged to the international clonal lineage IC2 (n = 27, 96.4%). Four isolates were considered tigecycline-intermediate (MIC = 2 mg/L), twenty-four isolates were tigecycline-resistant. The insertion of ISAba1 in adeS was found in six isolates and was the most prevalent insertion element (IS). In four isolates we observed an insertion of ISAba1 in adeN, and two of them had IS26 insertions. Two mutations in adeN (deletion and premature stop codon) were observed only in the MIC = 4 mg/L isolates. Other mutations in adeRS (amino acid insertion/substitutions and premature stop codons) were only detected in the MIC ≥ 8 group. The novel substitutions E219 K in adeR and A130 T in adeS were observed in five and four isolates respectively, suggesting a mutational hotspot. CONCLUSIONS: This study demonstrates that changes in transcription regulators were important mechanisms in tigecycline resistance in A. baumannii. Also, we identified several chromosomal hotspots that can be used for prediction of tigecycline resistance.

Cognitive function assessment and comparison on lateral ventricular tumors resection by the frontal transcortical approach and anterior transcallosal approach respectively in children.

Currently, there are few studies on cognitive impairment caused by neurosurgery, and there have been no studies on cognitive impairment after resection of lateral ventricular tumors in children. Previously, our research team has reported that the frontal transcortical approach can impair cognitive function. In this study, we explored which functions would be damaged by the transcallosal approach and compared the cognitive function changes caused by the two surgical approaches, so as to provide a theoretical basis for the selection of pre-operative surgical approaches. The authors prospectively collected pediatric patients with lateral ventricular tumors who had undergone surgical resection through the frontal transcortical approach and anterior transcallosal approach in Beijing Tiantan Hospital from November 2012 to May 2017. The inclusion criteria according to the Children Wechsler Scale requirements and clinical performance were formulated. Wechsler Intelligence Scale for Children®-fourth edition: Chinese version (WISC-IV) was adopted for general intelligence and cognitive function assessment in the study. In addition, the resting-state functional magnetic resonance imaging (resting-state fMRI) and diffusion tensor imaging (DTI) were carried out to measure the level of co-activation and to explore the functional connectivity between the brain regions at the pre-operative period and 6-month follow-up in post-operation. A total of 30 patients were enrolled. Gross total resection was achieved in all patients, and no severe post-operative complications were observed. The frontal transcortical approach was applied in 19 patients, and the transcallosal approach was conducted for 11 patients. Compared with the pre-operative indices of WISC-IV, patients generally had a lower level of indices of the WISC-IV in post-operation. In patients accepting lateral ventricular tumors resection through the anterior transcallosal approach, the total IQ was declined to M = 84.82, SD = 8.072 from M = 93.27, SD = 6.635 within the 6-month convalescence. The data of working memory (t = - 2.990, p = 0.002) and total IQ (t = - 2.205, p = 0.028) pre- and post-operative showed statistical significance. But in the comparison of two surgical approaches, it was found that IQ had no statistical difference in WISC-IV tasks data. Previous studies suggest that the frontal transcortical approach impair perceptual reasoning, processing speed, and IQ, while this study indicates that the anterior transcallosal approach impairs patients' working memory and IQ. Both approaches make equal damage to IQ. Through comparing the two surgical approaches, it can be known that the anterior transcallosal approach cannot replace the frontal transcortical approach. The protection of cognitive function should be considered as one of the bases for neurosurgeons to select the operative approach before the operation. However, in an actual situation, the specific approach should be carefully selected by comprehensive consideration.

Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44.

OBJECTIVE: As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism. DESIGN: A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity. The optical properties and biological effects were tested both in vitro and in vivo. The underlying mechanism was investigated using inhibitors, small interfering RNA (siRNA), RNA sequencing, mass spectrometry and human samples. RESULTS: We have screened and identified a new NIR autophagy-enhancer, IR-58, which exhibits significant tumour-selective killing effects. IR-58 preferentially accumulates in the mitochondria of colorectal cancer (CRC) cells and xenografts, a process that is glycolysis-dependent and organic anion transporter polypeptide-dependent. IR-58 kills tumour cells and induces apoptosis via inducing excessive autophagy, which is mediated through the reactive oxygen species (ROS)-Akt-mammalian target of rapamycin (mTOR) pathway. RNA sequencing, mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis induced by IR-58. TIM44 expression correlates positively with CRC development and poor prognosis in patients. CONCLUSIONS: A novel NIR small-molecule autophagy-enhancer, IR-58, with mitochondria-targeted imaging and therapy capabilities was developed for CRC treatment. Additionally, TIM44 was identified for the first time as a potential oncogene, which plays an important role in autophagy through the TIM44-SOD2-ROS-mTOR pathway.

The PPARγ agonist rosiglitazone sensitizes the BH3 mimetic (-)-gossypol to induce apoptosis in cancer cells with high level of Bcl-2.

The BH3 mimetic (-)-gossypol (-)-G has shown promising efficacy to kill several kinds of cancer cells or potentiate current chemotherapeutics. But it induces limited apoptosis in cancer cells with high level of Bcl-2. The nuclear receptor PPARγ and its agonist rosiglitazone can suppress various malignancies. More importantly, rosiglitazone is able to enhance the anti-tumor effects of chemotherapy drugs such as carboplatin and tyrosine kinase inhibitors. In this study, we for the first time demonstrated that rosiglitazone could sensitize (-)-G to induce apoptosis in cancer cells with high level of Bcl-2. Furthermore, we found that (-)-G increased the mRNA level and protein stability of Mcl-1, which weakened the pro-apoptotic effect of (-)-G. Rosiglitazone attenuated the (-)-G-induced Mcl-1 stability through decreasing JNK phosphorylation. Additionally, rosiglitazone upregulated dual-specificity phosphatase 16 (DUSP16), leading to a reduction of (-)-G-triggered JNK phosphorylation. Animal experiments showed that rosiglitazone could sensitize (-)-G to repress the growth of cancer cells with high level of Bcl-2 in vivo. Taken together, our results suggest that the PPARγ agonists may enhance the therapeutic effect of BH3 mimetics in cancers with high level of Bcl-2 through regulating the DUSP16/JNK/Mcl-1 singling pathway. This study may provide novel insights into the cancer therapeutics based on the combination of PPARγ agonists and BH3 mimetics.