Combination of electrochemical advanced oxidation and biotreatment for wastewater treatment and soil remediation.

The global concern surrounding the advancement of methods for treating wastewater and polluted soil has markedly increased over time. While electrochemical advanced oxidation processes (EAOPs) and biotreatments are commonly employed technologies for remediating wastewater and polluted soil, their widespread adoption is hindered by their limitations, which include high costs associated with EAOPs and prolonged remediation time of biotreatments. In the review, we provided an overview of EAOP technology and biotreatment, emphasizing the critical aspects involved in building a combined system. This review systematically evaluates recent research that combines EAOPs with bioremediation for treating wastewater or contaminated soil as pretreatment or post-treatment process. Research findings suggest that the combined treatment method represents a promising and competitive technology that can overcome some of the limitations of individual treatments. Additionally, we discussed the potential applications of this technology in varying levels of wastewater and soil pollution, as well as the underlying combination mechanisms.

Engineering dual-functional and thermophilic BMHETase for efficient degradation of polyethylene terephthalate.

Polyethylene terephthalate (PET) biodegradation is hindered by the intermediates bis (2-hydroxyethyl) terephthalate (BHET) and mono (2-hydroxyethyl) terephthalate (MHET). BMHETase, a thermophilic hydrolase identified from the UniParc database, exhibits degradation activity towards both BHET and MHET. BMHETase showed higher activity on BHET than LCCICCG and FASTPETase at temperatures ranging from 50 to 70℃. To enhance its activity in degrading MHET, BMHETase was engineered to mimic Ideonella sakaiensis MHETase. The resulting 6-point mutant's activities on MHET and BHET were 8 and 2 times those of the WT, with both optimal temperatures increased by 5℃. This enhancement may be attributed to the BMHETase6M's intensified binding ability with MHET and enlarged binding pocket. When combined with LCCICCG, BMHETase6M achieved complete degradation of MHET in PET films to terephthalic acid, indicating broad application potential. These findings suggest that BMHETase6M holds promise as a candidate for enhancing PET biodegradation efficiency and plastic waste management.

The fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils attenuates chronic atrophic gastritis induced by MNNG and its potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils is a commonly utilized traditional medicine among the Yi nationality, also known as "Gugongguo", for the treatment of gastrointestinal disorders. Previous studies have indicated that the extract of Rosa odorata sweet var. gigantea (FOE) fruit has demonstrated a protective effect on the stomach; however, its impact on chronic atrophic gastritis (CAG) with severe disease remains unknown. AIM OF THE STUDY: This study aimed to investigate the impact of FOE on CAG and its underlying mechanisms both in vitro and in vivo. MATERIALS AND METHODS: By employing Ultra Performance Liquid Chromatography/Quadrupole-Time of Flight Mass Spectrometry (UPLC-QTOF-MS/MS) and network pharmacology, the primary active compounds and action targets of FOE were identified. In vitro, the impact of FOE on CAG was investigated through scratch, migration, and invasion assays. Subsequently, guided by network pharmacology, EMT and TGF-ß signaling pathway-related proteins were assessed using Western blot and immunofluorescence experiments. Additionally, an in vivo CAG rat model was established to validate the effects of FOE and confirm its mechanism of action through hematoxylin-eosin (H&E), immunohistochemistry, Western blot, as well as untargeted metabolomics analysis of rat serum. It was observed that FOE inhibited scratch healing abilities, migration, invasion capabilities, as well as the expression of EMT-related proteins (E-cadherin, N-cadherin, Snail, Vimentin) in CAG model cells (MC cells), providing initial evidence for its efficacy. RESULTS: Through the analysis of UPLC-QTOF-MS/MS, a total of 51 major compounds were identified in the FOE. Subsequent network pharmacological analysis suggested that FOE may regulate Epithelial mesenchymal transition (EMT) through the transforming growth factor ß (TGF-ß) pathway. Furthermore, experimental verification demonstrated that FOE inhibited the protein expression of TGF-ß1 and its downstream protein Smad2/3 in vitro. In vivo findings also indicated similar mechanisms in MC cells, suggesting a reversal of the CAG process and significant inhibition of EMT and TGF-ß signaling pathways. Additionally, untargeted metabolomics of rat serum confirmed the therapeutic effect of FOE on CAG and predicted its potential involvement in the arachidonic acid metabolic pathway. CONCLUSION: This study initially demonstrated that FOE effectively reverses the process of EMT through the TGF-ß1/Smad2/3 signaling pathway, thereby providing a therapeutic benefit for CAG.

Effect of Real-Time Continuous Glucose Monitoring Versus Flash Glucose Monitoring on Glycemic Control in Adults with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aimed to compare the effect of the real-time continuous glucose monitoring (rt-CGM) and flash glucose monitoring (FGM) on glycemic control in adults with type 1 diabetes mellitus (T1DM). Methods: A systematic literature search of all relevant studies comparing the clinical effectiveness of rt-CGM and FGM in adults with T1DM on Cochrane Library, PubMed, Embase, Web of Science, and Scopus from January 2015 to June 2023 was performed. The primary endpoints were glycated hemoglobin (HbA1c) and TIR (time in range). Secondary endpoints included time below range [TBR (<3.9 mmol/L) and (<3.0 mmol/L)], time above range [TAR (>10.0 mmol/L) and (>13.9 mmol/L)], mean glucose, and glycemic variability (GV) [standard deviations (SD) and coefficient of variation (CV)]. Results: Six studies with 1516 TIDM patients, including three randomized controlled trials and three observational studies, were enrolled in this meta-analysis. Compared to FGM, rt-CGM led to greater glycemic control, represented by higher TIR (%, 3.9 ∼ 10 mmol/L) (SMD = 0.59, 95%CI: 0.37 ∼ 0.81, p < 0.001), decreased TBR (%, <3.9 mmol/L) (SMD = -1.45, 95%CI: -2.33 ∼ -0.57, p = 0.001), decreased TAR [(%, >10.0 mmol/L) (SMD = -0.38, 95%CI: -0.71 ∼ -0.04, p = 0.03) and (%, >13.9 mmol/L) (SMD = -0.42, 95%CI: -0.79 ∼ -0.04, p = 0.03), respectively], lower mean glucose (SMD = -0.18, 95%CI: -0.31 ∼ -0.06, p = 0.003), decreased SD (SMD = -0.70, 95%CI: -1.09 ∼ -0.31, p < 0.001), and decreased CV (SMD = -0.76, 95%CI: -1.05 ∼ -0.47, p < 0.001). However, there was no difference in lowering HbA1c and TBR (%, <3.0 mmol/L) between groups. Conclusion: The rt-CGM outperformed FGM in improving several key CGM metrics among adults with T1DM, but there is no significant difference in HbA1c and TBR (<3.0 mmol/L).

The prevalence of 12-month suicidal ideation and associated factors among university students in China: Findings from a three-wave cross-sectional study from 2021 to 2023.

BACKGROUND: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China. METHODS: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation. RESULTS: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation. LIMITATIONS: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students. CONCLUSIONS: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population.

Novel Insights into Enzymatic Thermostability: The "Short Board" Theory and Zero-Shot Hamiltonian Model.

Understanding the mechanism underlying thermostabilization in naturally stable enzymes and enhancing the thermostability of unstable enzymes are crucial aspects in enzyme engineering. Despite the development of various engineering methods, there remains substantial scope for improvement. In this study, a novel concept termed as the "short board" theory is proposed, which conceptualizes proteins as barrels with each component representing a jagged board. Notably, optimizing modifications to the shortest board yields optimal enhancements in terms of thermostability performance. To validate this theory, α-amylase, an industrial bulk enzyme with multiple domains, is employed as a model enzyme. The existence of "short boards" and their impact on thermostability modification are demonstrated at the domain, residue, and atomic levels through experimental confirmation using domain substitution. Furthermore, a novel thermostable design and prediction model called Zero-Shot Hamiltonian (ZSH) is established and evaluated on α-amylase. This coevolutionary approach based on thermostability and deep learning exhibits remarkable success exclusively when applied to enzymes with fixed short boards. The integration of the "short board" theory with the ZSH model presents an innovative tool for enhancing enzymatic thermostability.

The seed endophytic microbe Microbacterium testaceum M15 enhances the cold tolerance and growth of rice (Oryza sativa L.).

The potential of seed endophytic microbes to enhance plant growth and resilience is well recognized, yet their role in alleviating cold stress in rice remains underexplored due to the complexity of these microbial communities. In this study, we investigated the diversity of seed endophytic microbes in two rice varieties, the cold-sensitive CB9 and the cold-tolerant JG117. Our results revealed significant differences in the abundance of Microbacteriaceae, with JG117 exhibiting a higher abundance under both cold stress and room temperature conditions compared to CB9. Further analysis led to the identification of a specific cold-tolerant microbe, Microbacterium testaceum M15, in JG117 seeds. M15-inoculated CB9 plants showed enhanced growth and cold tolerance, with a germination rate increase from 40 % to 56.67 % at 14℃ and a survival rate under cold stress (4℃) doubling from 22.67 % to 66.67 %. Additionally, M15 significantly boosted chlorophyll content by over 30 %, increased total protein by 16.31 %, reduced malondialdehyde (MDA) levels by 37.76 %, and increased catalase activity by 26.15 %. Overall, our study highlights the potential of beneficial endophytic microbes like M. testaceum M15 in improving cold tolerance in rice, which could have implications for sustainable agricultural practices and increased crop productivity in cold-prone regions.

Acute effects of ambient nitrogen dioxide pollution on outpatient visits for neurological diseases in Xinxiang, China.

BACKGROUND: Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. METHODS: An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. RESULTS: A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45-2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. CONCLUSIONS: Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants.

The value of computed tomography angiography for evaluation of left atrial enlargement in patients with persistent atrial fibrillation.

BACKGROUND: The post-processing technology of CTA offers significant advantages in evaluating left atrial enlargement (LAE) in patients with persistent atrial fibrillation (PAF). This study aims to identify parameters for rapidly and accurately diagnosing LAE in patients with PAF using CT cross-sections. METHODS: Left atrial pulmonary venous (PV) CT was performed to 300 PAF patients with dual-source CT, and left atrial volume (LAV), left atrial anteroposterior diameter (LAD1), left atrial transverse diameter (LAD2), and left atrial area (LAA) were measured in the ventricular end systolic (ES) and middle diastolic (MD). LA index (LAI) = LA parameter/body surface area (BSA). Left atrial volume index (LAVIES) > 77.7 ml/m2 was used as the reference standard for the LAE diagnosis. RESULTS: 227 patients were enrolled in the group, 101 (44.5%) of whom had LAE. LAVES and LAVMD (r = 0.983), LAVIES and LAVIMD (r = 0.984), LAAES and LAVIES (r = 0.817), LAAMD and LAVIES (r = 0.814) had strong positive correlations. The area under curve (AUC) showed that all measured parameters were suitable for diagnosing LAE, and the diagnostic efficacy was compared as follows: LAA/LAAI> LAD> the relative value index of LAD, LAD2> LAD1. LAA and LAAI demonstrated comparable diagnostic efficacy, with LAA being more readily available than LAAI. CONCLUSIONS: The axial LAA measured by CTA can be served as a parameter for the rapid and accurate diagnosis of LAE in patients with PAF.

Noise-imitation learning: unpaired speckle noise reduction for optical coherence tomography.

Objective.Optical coherence tomography (OCT) is widely used in clinical practice for its non-invasive, high-resolution imaging capabilities. However, speckle noise inherent to its low coherence principle can degrade image quality and compromise diagnostic accuracy. While deep learning methods have shown promise in reducing speckle noise, obtaining well-registered image pairs remains challenging, leading to the development of unpaired methods. Despite their potential, existing unpaired methods suffer from redundancy in network structures or interaction mechanisms. Therefore, a more streamlined method for unpaired OCT denoising is essential.Approach.In this work, we propose a novel unpaired method for OCT image denoising, referred to as noise-imitation learning (NIL). NIL comprises three primary modules: the noise extraction module, which extracts noise features by denoising noisy images; the noise imitation module, which synthesizes noisy images and generates fake clean images; and the adversarial learning module, which differentiates between real and fake clean images through adversarial training. The complexity of NIL is significantly lower than that of previous unpaired methods, utilizing only one generator and one discriminator for training.Main results.By efficiently fusing unpaired images and employing adversarial training, NIL can extract more speckle noise information to enhance denoising performance. Building on NIL, we propose an OCT image denoising pipeline, NIL-NAFNet. This pipeline achieved PSNR, SSIM, and RMSE values of 31.27 dB, 0.865, and 7.00, respectively, on the PKU37 dataset. Extensive experiments suggest that our method outperforms state-of-the-art unpaired methods both qualitatively and quantitatively.Significance.These findings indicate that the proposed NIL is a simple yet effective method for unpaired OCT speckle noise reduction. The OCT denoising pipeline based on NIL demonstrates exceptional performance and efficiency. By addressing speckle noise without requiring well-registered image pairs, this method can enhance image quality and diagnostic accuracy in clinical practice.

Polyphenolic truxillic acid crosslinked sodium alginate film with notable antimicrobial and biodegradable properties for food packaging.

This work demonstrated an innovative antimicrobial and biodegradable food packaging film CBDA-10-SA which was prepared by crosslinking a natural polyphenolic truxillic acid (cyclobutane-dicarboxylic acid, CBDA-10) and sodium alginate (SA). The CBDA-10-SA film exhibited improved tensile strength (148 MPa) and UV shielding capabilities. The maximum thermal decomposition temperature was achieved of 249 °C. Compared to SA film, CBDA-10-SA showed increased antibacterial activities. In food packaging test, the CBDA-10-SA inhibited the rapid growth of potential of hydrogen (pH) value, slowed down the weight loss, reduced total plate count (TPC) value of pork, and delayed the spoilage process of pork. Notably, CBDA-10-SA displayed remarkable degradability in soil, with 60 % degrading in four weeks. In this study, CBDA-10-SA showed enhanced physicochemical and mechanical properties compared to traditional SA film. Those improvements make it anticipated to be used in not only food packaging but also mechanical, pharmaceutical, and agricultural fields.

Engineering a non-oxidative glycolysis pathway in escherichia coli for high-level citramalate production.

BACKGROUND: Methyl methacrylate (MMA) is a key precursor of polymethyl methacrylate, extensively used as a transparent thermoplastic in various industries. Conventional MMA production poses health and environmental risks; hence, citramalate serves as an alternative bacterial compound precursor for MMA production. The highest citramalate titer was previously achieved by Escherichia coli BW25113. However, studies on further improving citramalate production through metabolic engineering are limited, and phage contamination is a persistent problem in E. coli fermentation. RESULTS: This study aimed to construct a phage-resistant E. coli BW25113 strain capable of producing high citramalate titers from glucose. First, promoters and heterologous cimA genes were screened, and an effective biosynthetic pathway for citramalate was established by overexpressing MjcimA3.7, a mutated cimA gene from Methanococcus jannaschii, regulated by the BBa_J23100 promoter in E. coli. Subsequently, a phage-resistant E. coli strain was engineered by integrating the Ssp defense system into the genome and mutating key components of the phage infection cycle. Then, the strain was engineered to include the non-oxidative glycolysis pathway while removing the acetate synthesis pathway to enhance the supply of acetyl-CoA. Furthermore, glucose utilization by the strain improved, thereby increasing citramalate production. Ultimately, 110.2 g/L of citramalate was obtained after 80 h fed-batch fermentation. The citramalate yield from glucose and productivity were 0.4 g/g glucose and 1.4 g/(L·h), respectively. CONCLUSION: This is the highest reported citramalate titer and productivity in E. coli without the addition of expensive yeast extract and additional induction in fed-bath fermentation, emphasizing its potential for practical applications in producing citramalate and its derivatives.

Astragalus polysaccharides-induced gut microbiota play a predominant role in enhancing of intestinal barrier function of broiler chickens.

BACKGROUND: The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed. RESULTS: Dietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways). CONCLUSIONS: APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.

Global research trends on melasma: a bibliometric and visualized study from 2014 to 2023.

Melasma, a prevalent pigmentary disorder, is characterized by its complex etiology, propensity for recurrence, and resistance to treatment. However, there is currently no research on melasma through bibliometrics and visualisation. This study analyses the hotspots and trends in the field based on 2,709 publications from the Web of Science Core Collection (WOSCC). We carried out bibliometric analyses using Citespace software for different countries/regions, institutions, authors, and keywords. References were also analysed using VoSviewer. The results indicate that overall, there has been an increase in publications related to melasma since 2014. According to the analysis of the collaborative network diagram, the United States, Egyptian Knowledge Bank, and Benjakul Soottawat are the most contributing countries, institutions, and authors, respectively. Reference and keyword analyses have identified the pathogenesis and treatment of melasma as a prevalent topic in recent years. And how to find new treatment options and more effective therapeutic drugs is a future research trend. This is the first bibliometric and visual analysis of melasma-related literature to explore research hotspots and trends.

Insight into the Role of Rb Doping for Highly Efficient Kesterite Cu2ZnSn(S,Se)4 Solar Cells.

Various copper-related defects in the absorption layer have been a key factor impeding the enhancement of the efficiency of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Alkali metal doping is considered to be a good strategy to ameliorate this problem. In this article, Rb-doped CZTSSe (RCZTSSe) thin films were synthesized using the sol-gel technique. The results show that the Rb atom could successfully enter into the CZTSSe lattice and replace the Cu atom. According to SEM results, a moderate amount of Rb doping aided in enhancing the growth of grains in CZTSSe thin films. It was proven that the RCZTSSe thin film had the densest surface morphology and the fewest holes when the doping content of Rb was 2%. In addition, Rb doping successfully inhibited the formation of CuZn defects and correlative defect clusters and promoted the electrical properties of RCZTSSe thin films. Finally, a remarkable power conversion efficiency of 7.32% was attained by the champion RCZTSSe device with a Rb content of 2%. Compared with that of un-doped CZTSSe, the efficiency improved by over 30%. This study offers new insights into the influence of alkali metal doping on suppressing copper-related defects and also presents a viable approach for improving the efficiency of CZTSSe devices.

Phytic Acid-Gallium Network on a Polyimide Fiber Woven Fabric as an Artificial Ligament for Boosting Ligament-Bone Healing and Infection Treatment.

The development of an artificial ligament with a multifunction of promoting bone formation, inhibiting bone resorption, and preventing infection to obtain ligament-bone healing for anterior cruciate ligament (ACL) reconstruction still faces enormous challenges. Herein, a novel artificial ligament based on a PI fiber woven fabric (PIF) was fabricated, which was coated with a phytic acid-gallium (PA-Ga) network via a layer-by-layer assembly method (PFPG). Compared with PIF, PFPG with PA-Ga coating significantly suppressed osteoclastic differentiation, while it boosted osteoblastic differentiation in vitro. Moreover, PFPG obviously inhibited fibrous encapsulation and bone absorption while accelerating new bone regeneration for ligament-bone healing in vivo. PFPG remarkably killed bacteria and destroyed biofilm, exhibiting excellent antibacterial properties in vitro as well as anti-infection ability in vivo, which were ascribed to the release of Ga ions from the PA-Ga coating. The cooperative effect of the surface characteristics (e.g., hydrophilicity/surface energy and protein absorption) and sustained release of Ga ions for PFPG significantly enhanced osteogenesis while inhibiting osteoclastogenesis, thereby achieving ligament-bone integration as well as resistance to infection. In summary, PFPG remarkably facilitated osteoblastic differentiation, while it suppressed osteoclastic differentiation, thereby inhibiting osteoclastogenesis for bone absorption while accelerating osteogenesis for ligament-bone healing. As a novel artificial ligament, PFPG represented an appealing option for graft selection in ACL reconstruction and displayed considerable promise for application in clinics.

Spatial Proteomic Profiling of Colorectal Cancer Revealed Its Tumor Microenvironment Heterogeneity.

Colorectal cancer is a predominant malignancy with a second mortality worldwide. Despite its prevalence, therapeutic options remain constrained and surgical operation is still the most useful therapy. In this regard, a comprehensive spatially resolved quantitative proteome atlas was constructed to explore the functional proteomic landscape of colorectal cancer. This strategy integrates histopathological analysis, laser capture microdissection, and proteomics. Spatial proteome profiling of 200 tissue section samples facilitated by the fully integrated sample preparation technology SISPROT enabled the identification of more than 4000 proteins on the Orbitrap Exploris 240 from 2 mm2 × 10 µm tissue sections. Compared with normal adjacent tissues, we identified a spectrum of cancer-associated proteins and dysregulated pathways across various regions of colorectal cancer including ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Additionally, we conducted proteomic analysis on tumoral epithelial cells and paracancerous epithelium from early to advanced stages in hallmark rectum cancer and sigmoid colon cancer. Bioinformatics analysis revealed functional proteins and cell-type signatures associated with different regions of colorectal tumors, suggesting potential clinical implications. Overall, this study provides a comprehensive spatially resolved functional proteome landscape of colorectal cancer, serving as a valuable resource for exploring potential biomarkers and therapeutic targets.

Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus.

To investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC-MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury.

Sub-genomic RNAi-assisted strain evolution of filamentous fungi for enhanced protein production.

Genetic engineering at the genomic scale provides a rapid means to evolve microbes for desirable traits. However, in many filamentous fungi, such trials are daunted by low transformation efficiency. Differentially expressed genes under certain conditions may contain important regulatory factors. Accordingly, although manipulating these subsets of genes only can largely reduce the time and labor, engineering at such a sub-genomic level may also be able to improve the microbial performance. Herein, first using the industrially important cellulase-producing filamentous fungus Trichoderma reesei as a model organism, we constructed suppression subtractive hybridization (SSH) libraries enriched with differentially expressed genes under cellulase induction (MM-Avicel) and cellulase repression conditions (MM-Glucose). The libraries, in combination with RNA interference, enabled sub-genomic engineering of T. reesei for enhanced cellulase production. The ability of T. reesei to produce endoglucanase was improved by 2.8~3.3-fold. In addition, novel regulatory genes (tre49304, tre120391, and tre123541) were identified to affect cellulase expression in T. reesei. Iterative manipulation using the same strategy further increased the yield of endoglucanase activity to 75.6 U/mL, which was seven times as high as that of the wild type (10.8 U/mL). Moreover, using Humicola insolens as an example, such a sub-genomic RNAi-assisted strain evolution proved to be also useful in other industrially important filamentous fungi. H. insolens is a filamentous fungus commonly used to produce catalase, albeit with similarly low transformation efficiency and scarce knowledge underlying the regulation of catalase expression. By combining SSH and RNAi, a strain of H. insolens producing 28,500 ± 288 U/mL of catalase was obtained, which was 1.9 times as high as that of the parent strain.IMPORTANCEGenetic engineering at the genomic scale provides an unparalleled advantage in microbial strain improvement, which has previously been limited only to the organisms with high transformation efficiency such as Saccharomyces cerevisiae and Escherichia coli. Herein, using the filamentous fungus Trichoderma reesei as a model organism, we demonstrated that the advantage of suppression subtractive hybridization (SSH) to enrich differentially expressed genes and the convenience of RNA interference to manipulate a multitude of genes could be combined to overcome the inadequate transformation efficiency. With this sub-genomic evolution strategy, T. reesei could be iteratively engineered for higher cellulase production. Intriguingly, Humicola insolens, a fungus with even little knowledge in gene expression regulation, was also improved for catalase production. The same strategy may also be expanded to engineering other microorganisms for enhanced production of proteins, organic acids, and secondary metabolites.