Spatiotemporal characteristics of tissue derived small extracellular vesicles is associated with tumor relapse and anti-PD-1 response.

Small extracellular vesicles (sEVs) residing at tumor tissues are valuable specimens for biopsy. Tumor heterogeneity is common across all cancer types, but the heterogeneity of tumor tissue-derived sEVs (Ti-sEVs) is undefined. This study aims to discover the spatial distributions of Ti-sEVs in oral squamous cell carcinoma (OSCC) tissues and explore how these vesicle distributions affect the patients' prognosis. Multi-regional sampling enabled us to uncover that Ti-sEVs' accumulation at peritumoral sites correlates with a higher disease-free survival rate, and conversely, sparse peritumoral Ti-sEVs tend to forecast a higher risk of relapse. Of those relapsed patients, Ti-sEVs strongly bind to extracellular matrix and subsequently degrade it for allowing themselves enter the bloodstream rather than staying in situ. In advanced OSCC patients, the quantity and spatial distribution of Ti-sEVs prior to anti-PD-1 treatment, as well as the temporal variance of Ti-sEVs before and after immunotherapy, strongly map the clinical response and can help to distinguish the patients with shrinking tumors from those with growing tumors. Our work elucidates the correlation of spatiotemporal features of Ti-sEVs with patients' therapeutic outcomes and exhibit the potential for using Ti-sEVs as a predictor to forecast prognosis and screen the responders to anti-PD-1 therapy.

Asymmetric XMoGeY2 (X = S, Se, Te; Y = N, P, As) monolayers as potential flexible materials for nano piezoelectric devices and nanomedical sensors.

Highly efficient nano piezoelectric devices and nanomedical sensors are in great demand for high-performance piezoelectric materials. In this work, we propose new asymmetric XMoGeY2 (X = S, Se, Te; Y = N, P, As) monolayers with excellent piezoelectric properties, dynamic stability and flexible elastic properties. The piezoelectric coefficients (d11) of XMoGeY2 monolayers range from 2.92 to 8.19 pm V-1. Among them, TeMoGeAs2 exhibits the highest piezoelectric coefficient (d11 = 8.19 pm V-1), which is 2.2 times higher than that of common 2D piezoelectric materials such as 2H-MoS2 (d11 = 3.73 pm V-1). Furthermore, all XMoGeY2 monolayers demonstrate flexible elastic properties ranging from 96.23 to 253.70 N m-1. Notably, TeMoGeAs2 has a Young's modulus of 96.23 N m-1, which is only one-third of that of graphene (336 N m-1). The significant piezoelectric coefficients of XMoGeY2 monolayers can be attributed to their asymmetric structures and flexible elastic properties. This study provides valuable insights into the potential applications of XMoGeY2 monolayers in nano piezoelectric devices and nanomedical sensors.

Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain.

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

Genomic characterization and related functional genes of γ- poly glutamic acid producing Bacillus subtilis.

γ- poly glutamic acid (γ-PGA), a high molecular weight polymer, is synthesized by microorganisms and secreted into the extracellular space. Due to its excellent performance, γ-PGA has been widely used in various fields, including food, biomedical and environmental fields. In this study, we screened natto samples for two strains of Bacillus subtilis N3378-2at and N3378-3At that produce γ-PGA. We then identified the γ-PGA synthetase gene cluster (PgsB, PgsC, PgsA, YwtC and PgdS), glutamate racemase RacE, phage-derived γ-PGA hydrolase (PghB and PghC) and exo-γ-glutamyl peptidase (GGT) from the genome of these strains. Based on these γ-PGA-related protein sequences from isolated Bacillus subtilis and 181 B. subtilis obtained from GenBank, we carried out genotyping analysis and classified them into types 1-5. Since we found B. amyloliquefaciens LL3 can produce γ-PGA, we obtained the B. velezensis and B. amyloliquefaciens strains from GenBank and classified them into types 6 and 7 based on LL3. Finally, we constructed evolutionary trees for these protein sequences. This study analyzed the distribution of γ-PGA-related protein sequences in the genomes of B. subtilis, B. velezensis and B. amyloliquefaciens strains, then the evolutionary diversity of these protein sequences was analyzed, which provided novel information for the development and utilization of γ-PGA-producing strains.

A national survey on current state and development needs of clinical and academic emergency medicine in China.

BACKGROUND: To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. METHODS: An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. RESULTS: 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. CONCLUSIONS: EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Layered assembly of PEGylated graphene oxide and Mg-Al layered double hydroxide nanosheets with superior adsorption capacity and selective isolation of hemoglobin.

This study developed a novel organic-inorganic hybrid composite, shortly as GO-PEG-LDHs, by self-assembly of exfoliated Mg-Al layer double hydroxide (LDHs) on the polyethylene glycol (PEG) grafted graphene oxide (GO) to achieve the selective adsorption of hemoglobin (Hb). The prepared GO-PEG-LDHs has a hierarchical structure with a homogeneous loading of exfoliated LDHs nano-sheets on its surface. The adsorption test reveals that GO-PEG-LDHs exhibits an adsorption efficiency of 95.03% for Hb and 3.45% for bovine serum albumin (BSA). The adsorption of Hb follows the Langmuir model, with an ultrahigh adsorption capacity of 55248.6 mg/g, which is higher than any previously reported materials. Meanwhile, the adsorbed Hb can be efficiently recovered through elution with a 50 mM Tris-HCl buffer, with an elution efficiency of 80.77%. Circular dichroism (CD) spectra indicate no conformational change for Hb during the process of adsorption/desorption. Furthermore, the composite demonstrates the ability to selectively isolate Hb in the presence of interfering protein BSA, indicating its potential for practical applications.

3-methyl-1H-indol-1-yl dimethylcarbamodithioate attenuates periodontitis through targeting MAPK signaling pathway-regulated mitochondrial function.

Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.

The Impact of Ultrasound-Guided Combined with Water and Air Mixed Injection Method for Nasal Intestinal Tube Placement on Gastrointestinal Burden in Patients with Severe Acute Pancreatitis.

Objective: This study aims to investigate the impact of ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement on gastrointestinal burden in patients with severe acute pancreatitis. Methods: A cohort of 116 patients with severe acute pancreatitis admitted to the hospital from August 2021 to July 2023 were included. They were randomly divided into the control group (58 cases, nasal intestinal tube placement using ultrasound-guided combined water injection) and the observation group (58 cases, nasal intestinal tube placement using ultrasound-guided combined with water and air mixed injection). The incubation time, volume of water injected during the incubation, nasal intestinal tube visualization rate, and success rate of one-time incubation were recorded for both groups. Gastrointestinal mucosal barrier function, Nutritional index level including intestinal fatty acid-binding protein (I-FABP), D-lactate and nutritional index levels including hemoglobin (Hb), serum albumin (ALB), retinol-binding protein (RBP) were compared between the two groups before tube placement and at 7 days after incubation. Complications in both groups were also recorded. Results: The incubation time in the observation group was shorter, and the volume of water injected during the incubation was lower than in the control group. The nasal intestinal tube visualization rate and success rate of one-time incubation were higher in the observation group (P < .05). At 7 days after incubation, the levels of I-FABP and D-lactate were lower in the observation group than in the control group (P < .05). At 7 days after incubation, The levels of I-FABP and D-lactate in the observation group were lower than those in the control group, Hb and RBP levels were higher in the observation group than in the control group (P < .05), while there was no significant difference in ALB levels between the two groups (P > .05). The incidence of complications was lower in the observation group than in the control group (P < .05). Conclusion: Ultrasound-guided combined with water and air mixed injection method for nasal intestinal tube placement in patients with severe acute pancreatitis can shorten the incubation time, reduce the volume of water injected during the incubation, improve the nasal intestinal tube visualization rate and success rate of one-time incubation, enhance gastrointestinal mucosal barrier function and nutritional index in patients, and reduce the incidence of complications.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria.

Six new dimeric 2-(2-phenylethyl)chromones (1-6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1-6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8'') of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 µM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 µM.

Quercetin Enhances 5-fluorouracil Sensitivity by Regulating the Autophagic Flux and Inducing Drp-1 Mediated Mitochondrial Fragmentation in Colorectal Cancer Cells.

BACKGROUND: While chemotherapy treatment demonstrates its initial effectiveness in eliminating the majority of the tumor cell population, nevertheless, most patients relapse and eventually succumb to the disease upon its recurrence. One promising approach is to explore novel, effective chemotherapeutic adjuvants to enhance the sensitivity of cancer cells to conventional chemotherapeutic agents. In the present study, we explored the effect of quercetin on the sensitivity of colorectal cancer (CRC) cells to conventional chemotherapeutic agent 5-fluorouracil (5-FU) and the molecular mechanisms. METHODS: MTT assay, colony formation assay and Hoechst staining were performed to investigate the growth inhibition effect of quercetin alone or combined with 5-FU. The expression levels of apoptosis- and autophagy-related proteins were assessed by western blotting. Intracellular ROS was detected using DCFH-DA. The change in the mitochondrial membrane potential was measured by a JC-1 probe. The effect of quercetin on mitochondrial morphology was examined using a mitochondrial-specific fluorescence probe, Mito-Tracker red. RESULTS: The results demonstrated quercetin-induced apoptosis and autophagy, as well as imbalanced ROS, decreased mitochondrial membrane potential, and Drp-1-mediated mitochondrial fission in CRC cells. Autophagy blockage with autophagy inhibitor chloroquine (CQ) enhanced quercetininduced cytotoxicity, indicating that quercetin-induced cytoprotective autophagy. Meanwhile, quercetin enhanced the sensitivity of CRC cells to 5- FU via the induction of mitochondrial fragmentation, which could be further enhanced when the quercetin-induced protective autophagy was blocked by CQ. CONCLUSION: Our findings suggested that quercetin could induce protective autophagy and Drp-1-mediated mitochondrial fragmentation and enhance the sensitivity of CRC cells to conventional agent 5-FU, which not only suggests that quercetin may act as a chemotherapeutic adjuvant but also implies that the regulation of autophagic flux may be a potential therapeutic strategy for colorectal cancer.

Early ontogenesis from embryo to juvenile in Senegalese sole Solea senegalensis under laboratory conditions.

Senegalese sole, Solea senegalensis, is a flatfish of high commercial value in the world. It has been identified as an interesting and promising species for marine commercial aquaculture diversification in Europe for at least four decades and was introduced to China in 2003. Early ontogenesis from embryo to juvenile stages in S. senegalensis was analysed under controlled laboratory conditions to provide morphological information for aquaculture. From 0 to 59 days post hatching (dph), 10-20 larvae were sampled and measured each day (0-17 dph) or every 2-6 days (17-59 dph). Morphological characteristics from the egg to the juvenile stage were described. The eggs were separate and spherical with multiple oil globules. After 3 dph, the yolk sac was completely absorbed, mouth and anus were open, a swim bladder appeared, and larvae began feeding on rotifers (Brachionus plicatilis). The larvae began metamorphosis as the notochord flexed upward and the left eye migrated upward after 10 dph. The left eye migrated to the dorsal midline at 15 dph. At 19 dph, the left eye was translocated to the right-ocular side, and the juveniles adopted a benthic lifestyle. The swim bladder degenerated, and the juveniles completed metamorphosis at 23 dph. The growth patterns of some parameters (TL, SL, BH, BW) during larval and juvenile development stages were identified. The inflection points, which are slopes of growth changes, were calculated in growth curves. Three inflection points occurring in the growth curves of larvae and juveniles were found to be associated with metamorphosis, weaning, and transitions in feeding habits. The basic information of embryo development and ontogenesis in this study represents a valuable contribution to the S. senegalensis industry, especially in artificial breeding and rearing techniques.

The regulatory role of autophagy between TAMs and tumor cells.

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor-associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.

Generation of a ISL1 homozygous knockout stem cell line (WAe009-A-1G) by episomal vector-based CRISPR/Cas9 system.

The ISL LIM homeobox 1 (ISL1) gene belongs to the LIM/homeodomain transcription factor family and plays a pivotal role in conveying multipotent and proliferative properties of cardiac precursor cells. Mutations in ISL1 are linked to congenital heart disease. To further explore ISL1's role in the human heart, we have created a homozygous ISL1 knockout (ISL1-KO) human embryonic stem cell line using the CRISPR/Cas9 system. Notably, this ISL1-KO cell line retains normal morphology, pluripotency, and karyotype. This resource serves as a valuable tool for investigating ISL1's function in cardiomyocyte differentiation.

Assessment of rapid initiators and long-lasting nutrients for developing biological permeable reactive barriers to treat mine-contaminated groundwater.

The formation of mine-contaminated groundwater as a result of acidic mine drainage from the oxidation of sulfur-containing minerals entering the groundwater. Biological permeable reactive barrier (Bio-PRB) technology is excellent for the remediation of mine-contaminated groundwater. Usually, the organic substrates utilized in Bio-PRB are a combination of rapid initiators, which are readily bioavailable, and long-lasting nutrients, which are more difficult to degrade. Herein, we investigated the effectiveness of three rapid initiators and three long-lasting nutrients to remove sulfate from simulated mine-contaminated groundwater via simulated column experiments. The rapid initiators comprised crude glycerol, sodium acetate, and industrial syrup (IS), and the long-lasting nutrients included biodiesel emulsified oil, soybean oil emulsified oil, and high-carbon alcohol emulsified oil (HO). Microorganisms were stimulated using IS to create a sulfate reduction system owing to its high total organic carbon content (24.30 g L-1), achieving optimal sulfate removal rate (1.69 mmol dm-3 d-1). The fastest (2.93 mmol dm-3 d-1) and highest (88%) sulfate removal rates were achieved using HO, which is probably associated with the ability of HO to provide the most suitable C/N ratio (111.75) and induce the growth of sulfate-reducing bacteria (SRB) for substrate degradation. Conversely, a high concentration of sulfate reduction products inhibited SRB growth in the HO column. The addition of organic materials promoted SRB growth and various organic substrate-degrading bacteria. Furthermore, the competitive growth of methanogens (86.6%) may be responsible for the decrease in the relative abundance of SRB during the later stages of the experiment in the HO column.

RSAFormer: A method of polyp segmentation with region self-attention transformer.

Colonoscopy has attached great importance to early screening and clinical diagnosis of colon cancer. It remains a challenging task to achieve fine segmentation of polyps. However, existing State-of-the-art models still have limited segmentation ability due to the lack of clear and highly similar boundaries between normal tissue and polyps. To deal with this problem, we propose a region self-attention enhancement network (RSAFormer) with a transformer encoder to capture more robust features. Different from other excellent methods, RSAFormer uniquely employs a dual decoder structure to generate various feature maps. Contrasting with traditional methods that typically employ a single decoder, it offers more flexibility and detail in feature extraction. RSAFormer also introduces a region self-attention enhancement module (RSA) to acquire more accurate feature information and foster a stronger interplay between low-level and high-level features. This module enhances uncertain areas to extract more precise boundary information, these areas being signified by regional context. Extensive experiments were conducted on five prevalent polyp datasets to demonstrate RSAFormer's proficiency. It achieves 92.2% and 83.5% mean Dice on Kvasir and ETIS, respectively, which outperformed most of the state-of-the-art models.

[Effectiveness of unilateral biportal endoscopy combined with percutaneous pedicle screw fixation in treatment of lumbar burst fractures with neurological symptoms].

Objective: To evaluate the effectiveness of spinal canal decompression assisted by unilateral biportal endoscopy (UBE) and percutaneous uniplanar pedicle screw internal fixation in the treatment of lumbar burst fractures with neurological symptoms. Methods: Between June 2021 and December 2022, 10 patients with single level lumbar burst fracture with neurological symptoms were treated with spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw internal fixation. There were 7 males and 3 females with an average age of 43.1 years (range, 21-57 years). The injured vertebrae located at L 1 in 2 cases, L 2 in 4 cases, L 3 in 3 cases, and L 4 in 1 case. There were 7 cases of AO type A3 fractures and 3 cases of AO type A4 fractures. The total operation time, the time of operation under endoscopy, and complications were recorded. Pre- and post-operative visual analogue scale (VAS) score and American Spinal Injury Association (ASIA) scale (grading A-E corresponding to assigning 1-5 points for statistical analysis) were used to evaluate effectiveness. X-ray film and CT were performed to observe the fracture healing, and the ratio of anterior vertebral body height, Cobb angle, and rate of spinal canal invasion were measured to evaluate the reduction of fracture. Results: All operations was successfully completed, and the spinal canal decompression and the bone fragment in spinal canal reduction completed under the endoscopy. Total operation time was 119 minutes on average (range, 95-150 minutes), and the time of operation under endoscopy was 46 minutes on average (range, 35-55 minutes). There was no complication such as dural sac, nerve root, or blood vessel injury during operation. All incisions healed by first intention. All patients were followed up 18.7 months on average (range, 10-28 months). The VAS score after operation significantly decreased when compared with that before operation ( P<0.05), and further improved at last follow-up ( P<0.05). The ASIA scale after operation significantly improved when compared with that before operation ( P<0.05), and there was no significant difference ( P>0.05) in the ASIA scale between at 1 week after operation and at last follow-up. The imaging examination showed that the screw position was good and the articular process joint was preserved. During follow-up, there was no loosening, fracture, or fixation failure of the internal fixation. The ratio of anterior vertebral body height and Cobb angle significantly improved, the rate of spinal canal invasion significantly decreased after operation ( P<0.05), and without significant loss of correction during the follow-up ( P>0.05). Conclusion: Spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw fixation is a feasible minimally invasive treatment for lumbar burst fractures with neurological symptoms, which can effectively restore the vertebral body sequence, as well as relieve the compression of spinal canal, and improve the neurological function.

Prognostic and clinical significance of tumor-associated macrophages in esophageal squamous cell carcinoma after surgery: do biomarkers and distributions matter?

BACKGROUND: The role of tumor-associated macrophages (TAMs) in patients with esophageal squamous cell carcinoma (ESCC) following surgery remains controversial. Hence, we performed the present study to systematically analyze the prognostic and clinical significance of distinct TAMs biomarkers and distributions in ESCC patients underwent surgery. METHODS: PubMed, Web of Science, and EMBASE databases were searched up to March 31, 2023. The pooled analysis was conducted to evaluate the effects of TAMs on overall survival (OS), disease-free survival (DFS), and clinicopathological characteristics using fixed-effects or random-effect model. RESULTS: Involving a total of 2,502 ESCC patients underwent surgery from 15 studies, the results suggested that the total count of CD68+ TAMs was inversely associated with OS and DFS in ESCC patients, which was also noticed in the relationship of CD68+ TAMs in tumor islet (TI) with OS (all P<0.05), although no association between CD68+ TAMs in tumor stroma (TS) and OS (P>0.05). Moreover, either islet or stromal CD163+ TAMs density was a prognostic factor ESCC (all P<0.05). Similarly, an elevated CD204+ TAMs density in TI predicted a poor DFS (P<0.05), although CD204+ TAMs in TI had no relationship with OS (P>0.05). Besides, a high CD68+ TAMs density was significantly associated with lymphatic vessel invasion, vascular invasion, and lymph node metastasis (all P<0.05). CONCLUSION: Our results demonstrated the prognostic and clinical significance of TAMs in ESCC patients underwent surgery. TAMs should be considered a target that could improve prognostic stratification and clinical outcomes in ESCC after surgery.

Tropomyosin1 isoforms underlie epithelial to mesenchymal plasticity, metastatic dissemination, and resistance to chemotherapy in high-grade serous ovarian cancer.

Phenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure to specific environmental cues, represent the quintessential hallmark of the cancer cell en route from the primary lesion to distant organ sites where metastatic colonization will occur. Phenotypic plasticity is driven by a broad spectrum of epigenetic mechanisms that allow for the reversibility of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking advantage of the co-existence of epithelial and quasi-mesenchymal cells within immortalized cancer cell lines, we have analyzed the role of EMT-related gene isoforms in the regulation of epithelial mesenchymal plasticity (EMP) in high grade serous ovarian cancer. When compared with colon cancer, a distinct spectrum of downstream targets characterizes quasi-mesenchymal ovarian cancer cells, likely to reflect the different modalities of metastasis formation between these two types of malignancy, i.e. hematogenous in colon and transcoelomic in ovarian cancer. Moreover, upstream RNA-binding proteins differentially expressed between epithelial and quasi-mesenchymal subpopulations of ovarian cancer cells were identified that underlie differential regulation of EMT-related isoforms. In particular, the up- and down-regulation of RBM24 and ESRP1, respectively, represent a main regulator of EMT in ovarian cancer cells. To validate the functional and clinical relevance of our approach, we selected and functionally analyzed the Tropomyosin 1 gene (TPM1), encoding for a protein that specifies the functional characteristics of individual actin filaments in contractile cells, among the ovarian-specific downstream AS targets. The low-molecular weight Tpm1.8/9 isoforms are specifically expressed in patient-derived ascites and promote invasion through activation of EMT and Wnt signaling, together with a broad spectrum of inflammation-related pathways. Moreover, Tpm1.8/9 expression confers resistance to taxane- and platinum-based chemotherapy. Small molecule inhibitors that target the Tpm1 isoforms support targeting Tpm1.8/9 as therapeutic targets for the development of future tailor-made clinical interventions.

Modeling nitrogen removal performance based on novel microbial activity indicators in WWTP by machine learning and biological interpretation.

Modeling the pollutant removal performance of wastewater treatment plants (WWTPs) plays a crucial role in regulating their operation, mitigating effluent anomalies and reducing operating costs. Pollutants removal in WWTPs is closely related to microbial activity. However, there is extremely limited knowledge on the models accurately characterizing pollutants removal performance by microbial activity indicators. This study proposed a novel specific oxygen uptake rate (SOURATP) with adenosine triphosphate (ATP) as biomass. Firstly, it was found that SOURATP and total nitrogen (TN) removal rate showed similar fluctuated trends, and their correlation was stronger than that of TN removal rate and common SOURMLSS with mixed liquor suspended solids (MLSS) as biomass. Then, support vector regressor (SVR), K-nearest neighbor regressor (KNR), linear regressor (LR), and random forest (RF) models were developed to predict TN removal rate only with microbial activity as features. Models utilizing the novel SOURATP resulted in better performance than those based on SOURMLSS. A model fusion (MF) algorithm based on the above four models was proposed to enhance the accuracy with lower root mean square error (RMSE) of 2.25 mg/L/h and explained 75% of the variation in the test data with SOURATP as features as opposed to other base learners. Furthermore, the interpretation of predictive results was explored through microbial community structure and metabolic pathway. Strong correlations were found between SOURATP and the proportion of nitrifiers in aerobic pool, as well as between heterotrophic bacteria respiratory activity (SOURATP_HB) and the proportion of denitrifies in anoxic pool. SOURATP also displayed consistent positive responses with most key enzymes in Embden-Meyerhof-Parnas pathway (EMP), tricarboxylic acid cycle (TCA) and oxidative phosphorylation cycle. In this study, SOURATP provides a reliable indication of the composition and metabolic activity of nitrogen removal bacteria, revealing the potential reasons underlying the accurate predictive result of nitrogen removal rates based on novel microbial activity indicators. This study offers new insights for the prediction and further optimization operation of WWTPs from the perspective of microbial activity regulation.