Prognostic value of creatine kinase (CK)-MB to total-CK ratio in colorectal cancer patients after curative resection.

OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.

An artificial intelligence powered study of enlarged facial pore prevalence on one million Chinese from different age groups and its correlation with environmental factors.

BACKGROUND: Enlarged pores are amidst one of the top cosmetic concerns, especially among Chinese. Many small-group studies have been conducted in understanding their prevalence and beauty relevance. Nonetheless, population-level investigations are still lacking because of gaps in data collection and processing of large-scale studies. Owing to the recent technological advancement enabled by artificial intelligence, databases on the scale of millions can be processed and analyzed readily. MATERIALS AND METHODS: Powered by big data capabilities, revealed a number of novel trends on pore conditions among over-a-million Chinese participants recruited via the "You Look Great Today" mobile application. A scoring model was constructed, which demonstrated high consistency with conventional grading method from dermatologists. Environmental data (weather, air pollution, light at night satellite) were applied to correlate with pore severity. RESULTS: Intraclass correlations between the two scoring systems were strong, with coefficients ranging from 0.79 to 0.92 for different facial areas. Statistical differences in pore severity among all four facial areas (cheek, forehead, nose, and overall) were observed, with the cheek exhibiting the most severe pore condition. Interestingly, Chinese men suffer from more severe pore condition than females. Multiple environmental factors exhibited strong correlations with cheek pore severity and were statistically fitted into linear regressions. Specifically, incremental risk with Each Low Temperature, Low Humidity, And High Solar Exposure correlate to worse cheek pore conditions. Although the Pearson correlation was low between cheek pore severity and light at night, comparison between representative cities demonstrated that in geologically similar cities, higher light at night corresponds to more severe cheek pore conditions. CONCLUSION: Our study is showcasing a robust and reliable AI model in facial pore evaluation. More importantly, insights uncovered using this facile approach also bear significant cosmetic ramifications in treatment of pore enlargement.

Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis.

The inflammatory response induced by fine particulate matter (PM2.5), a common class of air pollutants, is an important trigger for the development of pulmonary fibrosis. However, the specific mechanisms responsible for this phenomenon are yet to be fully understood. To investigate the mechanisms behind the onset and progression of lung fibrosis owing to PM2.5 exposure, both rats and human bronchial epithelial cells were subjected to varying concentrations of PM2.5. The involvement of the PPARG/HMGB1/NLRP3 signaling pathway in developing lung fibrosis caused by PM2.5 was validated through the utilization of a PPARG agonist (rosiglitazone), a PPARG inhibitor (GW9662), and an HMGB1 inhibitor (glycyrrhizin). These outcomes highlighted the downregulation of PPARG expression and activation of the HMGB1/NLRP3 signaling pathway triggered by PM2.5, thereby eliciting inflammatory responses and promoting pulmonary fibrosis. Additionally, PM2.5 exposure-induced DNA hypermethylation of PPARG-encoding gene promoter downregulated PPARG expression. Moreover, the DNA methyltransferase inhibitor 5-azacytidine mitigated the hypermethylation of the PPARG-encoding gene promoter triggered by PM2.5. In conclusion, the HMGB1/NLRP3 signaling pathway was activated in pulmonary fibrosis triggered by PM2.5 through the hypermethylation of the PPARG-encoding gene promoter.

Vitamin B complex blocks the dust fall PM2 .5 -induced acute lung injury through DNA methylation in rats.

This study aimed to explore whether vitamin B complex (folic acid, B6 , and B12 ) could avert DNA methylation changes associated with inflammation induced by acute PM2.5 exposure. Sprague-Dawley rats were administered by gavage with different concentrations of vitamin B complex once a day for 28 days, and then by intratracheal instillation with saline or PM2.5 once every 2 days for three times. Vitamin B continued to be taken during the PM2.5 exposure. Rats were sacrificed 24 h after the last exposure. The results showed that vitamin B complex could block the pathological changes and injury in lungs induced by PM2.5 . Meanwhile, vitamin B complex could prevent the abnormal DNA methylation of IL-4 and IFN-γ to antagonize the imbalance of IL-4/IFN-γ associated with inflammation. It was further found that vitamin B complex could regulate DNA methyltransferases (DNMTs) and increase the S-adenosylmethionine (SAM)/S-Adenosyl-L-homocysteine (SAH) ratio to reverse the hypomethylation of genomic DNA and the abnormal DNA methylation of IL-4 and IFN-γ. In conclusion, vitamin B complex has a protective effect on acute lung injury by attenuating abnormal DNA methylation induced by PM2.5 in rats. This study may provide a new insight into the physiological function of vitamin B to prevent the health effects induced by PM2.5 .

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BACKGROUND: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. OBJECTIVE: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). METHODS: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. RESULTS: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. CONCLUSION: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

Safety and efficacy of intraoperative iodine-125 seed implantation brachytherapy for rectal cancer patients: A retrospective clinical research.

BACKGROUND: This pilot study was performed to evaluate the risk of anastomotic leakage (AL) and pelvic autonomic nerve dysfunction, and the effects of (125) I brachytherapy after intraoperative permanent implantation of iodine-125 seeds within the patients with rectal carcinoma. METHODS: In a cohort consisting of 80 rectal cancer patients who received potentially curative resection of rectal carcinoma with implantation of (125) I brachytherapy or radical resection of rectal carcinoma underwent total mesorectal excision. The incidences of AL, fecal incontinence, urinary dysfunction, and sexual dysfunction were calculated for comparison, and risk factors for these complications were analyzed by logistic regression. Rates of tumor recurrence and overall survival were evaluated. RESULTS: Six out of 17 (35.29%) patients in the (125) I implant group and 1 out of 34 (2.94%) patients in the non-implant group were complicated with AL (P = 0.006). The incidences of urinary dysfunction (P = 0.005) and fecal incontinence (P = 0.023) were significantly different between the two groups. Multivariate analyses revealed that (125) I brachytherapy was an independent risk factor for AL (odds ratio, 18.702; 95%CI, 1.802-194.062; P = 0.014) and urinary dysfunction (odds ratio, 4.340; 95%CI, 1.158-16.264; P = 0.029), respectively. At postoperative 2-year, the recurrence rates were 5.56% in the (125) I implant group and 9.09% in the non-implant group (P = 0.029). CONCLUSIONS: Intraoperative implantation of (125) I brachytherapy significantly increases the risk of AL, fecal incontinence, urinary dysfunction, and improves local control and do not improve overall survival after total mesorectal excision.

Pathological response following neoadjuvant immunotherapy and imaging characteristics in dMMR/MSI-H locally advanced colorectal cancer.

Background: In recent years, there has been significant research interest in immunotherapy for colorectal cancer (CRC). Specifically, immunotherapy has emerged as the primary treatment for patients with mismatch repair gene defects (dMMR) or microsatellite highly unstable (MSI-H) who have colorectal cancer. Yet, there is currently no data to support the practicality and safety of neoadjuvant immunotherapy for colorectal cancer with dMMR or MSI-H. Therefore, a study was conducted to identify the postoperative pathology, safety profile, and imaging features of patients with dMMR or MSI-H CRC following neoadjuvant immunotherapy. Methods: The retrospective study was carried out on patients with locally advanced or metastatic CRC who received immunotherapy at Sichuan Cancer Hospital, with approval from the hospital's ethics committee. The study aimed to assess the short-term effectiveness of immunotherapy by focusing on pathological complete response (pCR) as the primary outcome, while also considering secondary endpoints such as objective response rate, disease-free survival, and safety profile. Results: Twenty patients with dMMR/MSI-H CRC who underwent neoadjuvant immunotherapy as part of the treatment were enrolled between May 2019 and February 2024 at Sichuan Cancer Hospital. Out of these patients, eight patients received PD-1 blockade monotherapy as neoadjuvant treatment, while 12 were administered a combined therapy of anti-CTLA-4 and anti-PD-1. 12 patients received Nivolumab plus Ipilimumab regimen and 8 patients received PD-1 blockades (2 patients were Pembrolizumab, 2 patients were Sintilimab, 4 patients were Tislelizumab) monotherapy. Additionally, 19 patients underwent surgery after immunotherapy and of these, 15 (75.0%) achieved complete pathological response (pCR), 8 (66.7%) achieved the same on Nivolumab plus Ipilimumab immunotherapy while 7 (87.5%) achieved on PD-1 antibody monotherapy. The overall response rate (ORR) was 75%, with 45.0% of patients experiencing grade I/II immunotherapy-related adverse events. The most frequent adverse event observed was increased ALT i.e. 20%. Notably, no postoperative complications were observed. Conclusion: Based on the findings, neoadjuvant immunotherapy for colorectal cancer may be both safe and effective in clinical practice. Furthermore, the study suggested that dual immunotherapy could potentially increase the immunotherapy cycle and contribute to a superior pCR rate. However, the conclusion emphasized the need for further prospective clinical trials to validate these results.

Contrastive machine learning reveals Parkinson's disease specific features associated with disease severity and progression.

Parkinson's disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

Outdoor tubular photobioreactor microalgae-microorganisms biofilm treatment of municipal wastewater: Enhanced heterotrophic assimilation and synergistic aerobic denitrogenation.

This research evaluated a microalgae consortium (MC) in a pilot-scale tubular photobioreactor for municipal wastewater (MWW) treatment, compared with an aeration column photobioreactor. Transitioning from suspended MC to a microalgae-microbial biofilm (MMBF) maintained treatment performance despite increasing influent from 50 L to 150 L in a 260 L system. Carbon and nitrogen removal were effective, but phosphorus removal varied due to biofilm shading and the absence of phosphorus-accumulating organisms. High influent flow caused MMBF detachment due to shear stress. Stabilizing and re-establishing the MMBF showed that a stable phycosphere influenced microbial diversity and interactions, potentially destabilizing the MMBF. Heterotrophic nitrification-aerobic denitrification bacteria were crucial for MC equilibrium. Elevated gene expression related to nitrogen fixation, organic nitrogen metabolism, and nitrate reduction confirmed strong microalgal symbiosis, highlighting MMBF's treatment potential. This study supports the practical application of microalgae in wastewater treatment.

Higher cortical excitability to negative emotions involved in musculoskeletal pain in Parkinson's disease.

OBJECTIVE: Changes in brain structure and neurotransmitter systems are involved in pain in Parkinson's disease (PD), and emotional factors are closely related to pain. Our study applied electroencephalography (EEG) to investigate the role of emotion in PD patients with chronic musculoskeletal pain. METHODS: Forty-two PD patients with chronic musculoskeletal pain and 38 without were enrolled. EEG data were recorded under resting conditions, and while viewing pictures with neutral, positive, and negative content. We compared spectrum power, functional connectivity, and late positive potential (LPP), an event-related potential (ERP), between the groups. RESULTS: PD patients with pain tended to have higher scores for the Hamilton Rating Scale for Depression (HRSD). In the resting EEG, mean ß-band amplitude was significantly higher in patients with pain than in those without. Logistic regression analysis showed that higher HRSD scores and higher mean ß-band amplitude were associated with pain. ERP analysis revealed that the amplitudes of LPP difference waves (the absolute difference between positive and negative condition LPP and neutral condition LPP) at the central-parietal region were significantly reduced in patients with pain (P = 0.029). Spearman correlation analysis showed that the amplitudes of late (700-1000 ms) negative versus neutral condition LPP difference waves were negatively correlated with pain intensity, assessed by visual analogue scale, (r = -0.393, P = 0.010) and HRSD scores (r = -0.366, P = 0.017). CONCLUSION: Dopaminergic and non-dopaminergic systems may be involved in musculoskeletal pain in PD by increasing ß-band activity and weakening the connection of the θ-band at the central-parietal region. PD patients with musculoskeletal pain have higher cortical excitability to negative emotions. The changes in pain-related EEG may be used as electrophysiological markers and therapeutic targets in PD patients with chronic pain.

The association and prognostic value of systemic inflammatory response index with short and long-term mortality in patients with sepsis.

This study evaluated the association and prognostic significance of the systemic inflammation response index (SIRI) with mortality in sepsis. In this cohort study, the sepsis patients were retrieved from the Medical Information Mart for Intensive Care III (MIMIC-III) and MIMIC-IV intensive care unit (ICU) databases. SIRI was calculated by using the neutrophil, monocyte, and lymphocyte counts. The outcomes were 28-day mortality, 1-year mortality, and 28 days to 1-year mortality. The Cox proportional hazards model with a hazard ratio (HR) and a 95% confidence interval (CI) was used to investigate the association and prognostic value of SIRI with mortality in sepsis. Subgroup analyses of the associations of SIRI with 28-day and 1-year mortality in sepsis were based on age, gender, Simplified Acute Physiology Score II (SAPSII), Sequential Organ Failure Assessment (SOFA), and presence or absence of septic shock. The receiver operating characteristic (ROC) curve was used to compare the predictive performances of SIRI, SOFA and SAPS II for mortality in sepsis. Of the 4239 patients included, 1339 patients suffered from 28-day mortality, 2085 patients suffering from 1-year mortality, and 746 (25.72%) suffered from 28 days to 1-year mortality. High SIRI levels exhibited higher risks of 28-day mortality (HR: 1.15, 95% CI: 1.03-1.29, P = .010), 1-year mortality (HR: 1.14, 95% CI: 1.04-1.24, P = .003), and 28 days to 1-year mortality (HR: 1.16, 95% CI: 1.01-1.35, P = .047) in sepsis. A higher SIRI was reported related to 28-day mortality and 1-year mortality in sepsis patients with female gender, with SOFA < 8, with SAPS II < 44, and in sepsis patients without sepsis shock. The AUC of SIRS, SOFA, and SAPS II in predicting 28-day mortality in sepsis were 0.726, 0.591, and 0.644, respectively. The AUC of SIRI in predicting 1-year mortality in sepsis was 0.761, higher than the AUC values of SOFA and SAPS II. A higher AUC value of SIRI compared with SOFA, and SAPS II in predicting 28 days to 1-year mortality was observed. Elevated SIRI was associated with an increased risk of mortality in sepsis. SIRI is an independent prognostic biomarker of mortality in sepsis.

Synthesis of temperature- and humidity-induced dual stimulation film PU-PNIPAm n and its independent film formation as a smart window application.

Dynamic windows, which switch between transparent and opaque states as the temperature changes, can be applied in buildings to reduce building energy consumption. Poly(N-isopropylacrylamide) (PNIPAm) is the most studied thermochromic hydrogel for climate-resilient smart window applications. In addition to its poor mechanical properties and low reaction rate, the PNIPAm hydrogel must be sandwiched between two pieces of glass to form an interlayer in practical applications. Here, durable PU-PNIPAm n copolymers for smart windows were synthesized by reacting the synthesized poly-NIPAm diols with isocyanate (-NCO) monomer, which greatly improved the mechanical properties of the hydrogel and it was able to form a film alone. These temperature-sensitive films can switch between transparent (>80% transmittance) and opaque (<5% transmittance) states in less than 10 minutes, with no degradation in optical contrast, switching speed, or uniformity after at least 100 switching cycles.

High-Strength Ductility Joining of Multicomponent Alloy to 304 Stainless Steel Using Laser Welding Technique.

In this work, a series of multicomponent alloys (CoCrFeNi, CoCrNi, and CoNiV) were laser welded with 304 stainless steel (304ss), and detailed comparisons on microstructural characteristics and mechanical properties were conducted for dissimilar laser welded joints. It is revealed that all of the dissimilar laser welded samples possessed defect-free joints and the corresponding fusion zone consisting of fcc single-phase showed homogeneous element distribution accompanied by a narrow element gradient in the vicinity of the fusion zone boundary. After laser welding with identical welding parameters, equiaxed grain was observed on the side of multicomponent alloy, while coarse columnar grain was obtained on the side of 304ss. Especially, the columnar grains of the fusion zone on the side of 304ss disclosed preferential <001> growth direction in the CoCrFeNi/304ss and CoCrNi/304ss welded joints. Furthermore, all of the dissimilar laser welded joints were fractured in the fusion zone, attributing to the drastic loss of strength in the fusion zone with coarsened grain. It is worth noting that a special lamellar structure that merged by dimples was found in the fracture surface of the CoNiV/304ss joint, closely related to the existence of the V-enriched region. Finally, a high strength-ductile synergy can be achieved by laser welding CoNiV alloy to 304ss, which showed a yield strength of 338 MPa, ultimate tensile strength of 686 MPa, and total elongation of 28.9%. These excellent mechanical properties prevailed in the potential of a CoNiV/304ss laser welded joint to be applied as a structural material.

Nocaviogua A and B: two lipolanthines from root-nodule-associated Nocardia sp.

Nocaviogua A (1) and B (2), two lipolanthines featuring a non-canonical avionin (Avi)-containing macrocycle and a long acyl chain, were identified from the mutualistic actinomycete Nocardia sp. XZ19_369, which was isolated from the nodules of sea buckthorn collected in Tibet. Their planar structures were elucidated via extensive analyses of 1D and 2D NMR, as well as HRMS data. The absolute configurations were fully elucidated by advanced Marfey's analysis and GIAO NMR calculations, representing the first time that the configurations of this family of lipolanthines have been determined. Nocaviogua A (1) exhibited weak cytotoxicity against human chronic uveal melanoma cells (UM92-1), non-small cell lung cancer (NCI-H2170), and breast cancer (MDA-MB-231). Our work provides valuable information on this burgeoning class of lipolanthines for further investigations.

How sleep quality affects activities of daily living in Parkinson's disease: the mediating role of disease severity and the moderating role of cognition.

Objective: The aim of this study was to explore the influential mechanism of the relationship between sleep quality and activities of daily living (ADL) in patients with Parkinson's disease (PD), we hypothesized disease severity as a mediator and assumed the mediating process was regulated by cognition. Methods: 194 individuals with PD (95 women and 99 men) were enrolled in study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality of PD patients. Patients' ADL, disease severity and cognition were measured by the Unified Parkinson's Disease Rating Scale-II (UPDRSII), Hoehn-Yahr (H-Y) Scale, and Mini-Mental State Examination (MMSE). We investigated the mediating role of disease severity and the moderating effect of cognition on the association between sleep quality and ADL in PD patients. Results: The score of UPDRSII was positively correlated with the score of PSQI and H-Y stage, while the score of MMSE was negatively correlated with the score of H-Y stage and UPDRSII. Sleep quality predicts disease severity, and disease severity predicts ADL. Disease severity mediated the relationship between sleep quality and ADL, and the mediating effect was 0.179. Cognition alone did not affect ADL, but the interaction between disease severity and cognition was significantly affected ADL, confirming the moderating effect of cognition in PD patients. Conclusion: Disease severity mediated the association between sleep quality and ADL, good cognition significantly reduced disease severity's mediating influence on the relationship between sleep quality and ADL. Our study indicated a close relationship between ADL and sleep and cognition in PD, and also provided new insights into the overall management of PD and a better quality of life of PD patients.

Myocardin-related transcription factor A, regulated by serum response factor, contributes to diabetic cardiomyopathy in mice.

AIMS: Diabetic cardiomyopathy is a significant contributor to the global pandemic of heart failure. In the present study we investigated the involvement of myocardin-related transcription factor A (MRTF-A), a transcriptional regulator, in this process. MATERIALS AND METHODS: Diabetic cardiomyopathy was induced in mice by feeding with a high-fat diet (HFD) or streptozotocin (STZ) injection. KEY FINDINGS: We report that MRTF-A was up-regulated in the hearts of mice with diabetic cardiomyopathy. MRTF-A expression was also up-regulated by treatment with palmitate in cultured cardiomyocytes in vitro. Mechanistically, serum response factor (SRF) bound to the MRTF-A gene promoter and activated MRTF-A transcription in response to pro-diabetic stimuli. Knockdown of SRF abrogated MRTF-A induction in cardiomyocytes treated with palmitate. When cardiomyocytes conditional MRTF-A knockout mice (MRTF-A CKO) and wild type (WT) mice were placed on an HFD to induce diabetic cardiomyopathy, it was found that the CKO mice and the WT mice displayed comparable metabolic parameters including body weight, blood insulin concentration, blood cholesterol concentration, and glucose tolerance. However, both systolic and diastolic cardiac function were exacerbated by MRTF-A deletion in the heart. SIGNIFICANCE: These data suggest that MRTF-A up-regulation might serve as an important compensatory mechanism to safeguard the deterioration of cardiac function during diabetic cardiomyopathy.

LINC01268 promotes epithelial-mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS.

BACKGROUND: Long non-coding RNAs (lncRNAs) with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer (GC), but their specific mechanisms and roles still need to be further elucidated. AIM: To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression. METHODS: Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues, cell lines and plasma. The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients. An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC. Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells. The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate (MARCKS), the PI3K/Akt signaling pathway, and the epithelial-mesenchymal transition (EMT) process in GC was demonstrated by western blot analysis. RESULTS: The expression of LINC01268 was increased in GC tissues and cell lines. The expression level of LINC01268 was significantly correlated with lymph node metastasis, TNM stage, and tumor differentiation in patients with GC. Over-expression of LINC01268 indicated a poor prognosis for patients with GC, and it had a certain auxiliary diagnostic value for GC. In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC. CONCLUSION: This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS, and ultimately promotes the invasion and metastasis of GC. LINC01268 may be a potential effective target for the treatment of GC.

Pairing comparative genomics with tandem mass-based molecular networking allows to highly efficient discovery of nonribosomal peptides from Nocardia spp.

Microbial natural products, particularly nonribosomal peptides (NRPs), have attracted significant attention due to their structural diversity and therapeutic potential. Nocardia, a genus of Actinomyces, is an important reservoir for natural products, especially NRPs. However, rediscovery is a significant challenge for mining new specialized metabolites from Nocardia, as well as from other sources. To overcome this challenge, we developed a strategy that combines comparative genomics with tandem mass-based molecular networking, which allows to efficiently discover new NRPs from Nocardia spp.. As a proof of concept, all genomes of Norcardia in NCBI database, including three strains from our lab, were compared with each other to prioritize unique biosynthetic gene clusters (BGCs) in the three in-house Nocardia strains, particularly those containing nonribosomal peptide synthases (NRPSs). Subsequently, the metabolomics data of those three in-house strains were analyzed employing tandem mass-based molecular networking. This led to the identification of a known lipopeptide, nocarjamide (1), and five new congeners (2-6) of nocarjamide, as well as a new decalipopeptide, nocarlipoamide (7), along with nocardimicin, a known compound found in Nocardia. The structure of the new decalipopeptide 7 was further extensively characterized using NMR, MS/MS, Marfey's analysis, and X-ray. In addition, the biosynthesis pathways for 1-7 were proposed through bioinformatics analysis, and thus the gene clusters responsible for biosynthesizing them were confirmed. Our results indicate that this strategy enables prompt dereplication of known compounds, rapid linkage of identified compounds with their biosynthesis gene cluster, and efficient discovery of new compounds.

Insights of microalgal municipal wastewater treatment at low temperatures: Performance, microbiota patterns, and cold-adaptation of tubular and aeration column photobioreactors.

In order to refine the treatment of microalgae consortium (MC) for municipal wastewater (MWW) during the winter, this study investigated the effectiveness of tubular and aeration column photobioreactors (TPBR and APBR) in wastewater treatment plant (WWTP) during winter by two start-up modes: microalgae/microalgae-activated sludge (AS). The operation results showed that under 5.7-13.1 °C, TPBR enhanced the assimilation of N and P pollutant by microalgal accumulation, meeting the Chinese discharge standard within 24 h (NH4+-N, TP, and COD ≤8.0, 0.5, and 50 mg·L-1). The microbial community profiles were identified and showed that inoculating AS under low-temperature still promoted bacterial interspecific association, but influenced by the inhibition of microbial diversity by the homogeneous circulation of TPBR, the nitrogen transfer function of MC was lower than that of APBR at low temperatures, except nitrogen fixation (K02588), nitrosification (K10944, K10945, and K10946), assimilatory nitrate reduction (K00366), and ammonification (K01915 and K05601). And the intermittent aeration in the APBR was still beneficial in increasing microbial diversity, which was more beneficial for reducing COD through microbial collaboration. In the treatment, the cryotolerant MGPM were Delftia, Romboutsia, Rhizobiales, and Bacillus, and the cold stress-related genes that were highly up-regulated were defense signaling molecules (K03671 and K00384), cold shock protein gene (K03704), and cellular protector (K01784) were present in both PBRs. This study provided a reference for the feasibility of the low temperature treatment of MC with the different types of PBR, which improved the application of wastewater treatment in more climatic environments.