Dietary Clostridium autoethanogenum protein has dose-dependent influence on the gut microbiota, immunity, inflammation and disease resistance of abalone Haliotis discus hannai.

Clostridium autoethanogenum protein (CAP) is an eco-friendly protein source and has great application potential in aquafeeds. The present study aimed to investigate the effects of dietary CAP inclusion on the anti-oxidation, immunity, inflammation, disease resistance and gut microbiota of abalone Haliotis discus hannai after a 110-day feeding trial. Three isonitrogenous and isolipidic diets were formulated by adding 0% (control), 4.10% (CAP4.10) and 16.25% (CAP16.25) of CAP, respectively. A total of 540 abalones with an initial mean body weight of 22.05 ± 0.19 g were randomly distributed in three groups with three replicates per group and 60 abalones per replicate. Results showed that the activities of superoxide dismutase and glutathione peroxidase in the cell-free hemolymph (CFH) were significantly decreased and the content of malondialdehyde in CFH was significantly increased in the CAP16.25 group. The diet with 4.1% of CAP significantly increased the activities of lysozyme and acid phosphatase in CFH. The expressions of pro-inflammatory genes such as tumor necrosis factor-α (tnf-α), nuclear factor-κb (nf-κb) and toll-like receptor 4 (tlr4) in digestive gland were downregulated, and the expressions of anti-inflammatory genes such as ß-defensin and mytimacin 6 in digestive gland were upregulated in the CAP4.10 group. Dietary CAP inclusion significantly decreased the cumulative mortality of abalone after the challenge test with Vibrio parahaemolyticus for 7 days. Dietary CAP inclusion changed the composition of gut microbiota of abalone. Besides, the balance of the ecological interaction network of bacterial genera in the intestine of abalone was enhanced by dietary CAP. The association analysis showed that two bacterial genera Ruegeria and Bacteroides were closely correlated with the inflammatory genes. In conclusion, the 4.10% of dietary CAP enhanced the immunity and disease resistance as well as inhibited the inflammation of abalone. The 16.25% of dietary CAP decreased the anti-oxidative capacity of abalone. The structure of the gut microbiota of abalone changed with dietary CAP levels.

Comprehensive pan-cancer analysis reveals that C5orf34 regulates the proliferation and mortality of lung cancer.

The gene C5orf34 exhibits evolutionary conservation among mammals, and emerging evidence suggests its potential involvement in tumor development; however, comprehensive investigations of this gene are lacking. This study aims to elucidate the functional attributes and underlying mechanisms of C5orf34 in cancer. To evaluate its clinical predictive value, we conducted an analysis of the pan-cancerous expression, clinical data, mutation, and methylation data of C5orf34. Additionally, we investigated the correlation between C5orf34 and tumor mutant load (TMB), immune cell infiltration, and microsatellite instability (MSI) through relevant analyses. Furthermore, immunohistochemical (IHC) staining was employed to validate clinical samples, while knockdown and overexpression experiments and transcriptome RNA sequencing were utilized to examine the impact of C5orf34 on LUAD cells. According to our study, C5orf34 exhibits high expression levels in the majority of malignant tumors. The upregulation of C5orf34 is governed by DNA copy number alterations and methylation patterns, and it is closely associated with patients' survival prognosis and immune characteristics, thereby holding significant clinical implications. Furthermore, IHC staining analysis, cellular experiments, and transcriptome RNA sequencing have provided evidence supporting the role of C5orf34 in modulating the cell cycle to promote LUAD proliferation, migration, and invasion. This highlights its potential as a promising therapeutic target. The findings of this investigation suggest that C5orf34 may serve as a valuable biomarker for various tumor types and represent a potential target for immunotherapy, particularly in relation to the proliferation, migration, and apoptosis of LUAD cells.

Indocyanine green fluorescence imaging technology for the treatment of chylothorax after oesophageal cancer: A case report.

Chylothorax is a serious postoperative complication of oesophageal cancer, and to date, there is no standardized and effective intraoperative diagnostic tool that can be used to identify the thoracic duct and determine the location of lymphatic fistulas. A 50-year-old patient with oesophageal squamous cell carcinoma developed chylothorax after thoracolaparoscopy combined with radical resection of oesophageal cancer. Twelve hours after surgery, 1200 mL of clear fluid was drained from the thoracic drainage tube, and a chyle test was sent. A thoracothoracic duct ligation procedure was performed on the first day after surgery. Although fluid accumulating in the posterior mediastinum was observed, the location of the lymphatic fistula could not be determined. During the surgery, indocyanine green (ICG) was injected into the bilateral inguinal lymph nodes, and a fluorescent lens was used to determine the location of the lymphatic fistula so the surgeon could ligate the thoracic duct. ICG fluorescence imaging technology can help surgeons effectively manage chylothorax after oesophageal cancer surgery. To our knowledge, this is the first report to describe the use of ICG fluorescence imaging technology to treat postoperative chylothorax in patients with oesophageal cancer in China.

LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop.

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.

Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer.

Ferroptosis is recognized as a new type of regulated cell death initiated by iron-dependent accumulation of lipid peroxidation. Recent studies have shown that the administration of ascorbic acid (AA) preferentially kills tumor cells by impairing iron metabolism and exerting pro-oxidant effects. Despite mounting evidence indicating the anticancer potential of AA, the underlying molecular mechanisms remain unknown. In this study, we demonstrated that AA decreased cell viability and Ki67 expression, along with its accumulation in the G0/G1 phase in FaDu and SCC-154 cell lines. Furthermore, AA exposure induced morphological changes in mitochondria associated with ferroptosis. AA-induced ferroptosis is accompanied by depletion of glutathione (GSH) and increased levels of ferrous ions (Fe2+), reactive oxygen species (ROS), and malondialdehyde (MDA). However, these ferroptotic effects were ameliorated by deferoxamine and N-acetylcysteine. Network pharmacology results showed that signal transducer and activator of transcription 3 (STAT3) is a key target of AA against oropharyngeal cancer. AA markedly downregulates the relative mRNA expression of STAT3 and glutathione peroxidase 4 (GPX4). Immunoblotting indicated that the protein levels of p-STAT3, STAT3, and GPX4 in FaDu and SCC-154 cells decreased significantly in response to AA treatment. Mechanistically, a chromatin immunoprecipitation assay confirmed that AA exposure reduced STAT3 expression in the GPX4 promoter region. Additionally, AA-induced inhibition of cell growth and ferroptosis was suppressed by STAT3 and GPX4 overexpression, respectively. In summary, AA inhibited oropharyngeal cancer cell growth in vitro by regulating STAT3/GPX4-mediated ferroptosis, which may provide a novel theoretical basis for the clinical treatment of oropharyngeal cancer with AA.

Ascorbic acid acts as an anticancer agent by inducing ferroptosis, reducing the viability of SCC-154 and FaDu cells.Ascorbic acid-mediated ferroptosis acts through STAT3/GPX4 pathway.The induction of ferroptosis has a significant potential for cancer therapy.

Rapid automated extracellular vesicle isolation and miRNA preparation on a cost-effective digital microfluidic platform.

As a prerequisite for extracellular vesicle (EV) -based studies and diagnosis, effective isolation, enrichment and retrieval of EV biomarkers are crucial to subsequent analyses, such as miRNA-based liquid biopsy for non-small-cell lung cancer (NSCLC). However, most conventional approaches for EV isolation suffer from lengthy procedure, high cost, and intense labor. Herein, we introduce the digital microfluidic (DMF) technology to EV pretreatment protocols and demonstrate a rapid and fully automated sample preparation platform for clinical tumor liquid biopsy. Combining a reusable DMF chip technique with a low-cost EV isolation and miRNA preparation protocol, the platform completes automated sample processing in 20-30 min, supporting immediate RT-qPCR analyses on EV-derived miRNAs (EV-miRNAs). The utility and reliability of the platform was validated via clinical sample processing for EV-miRNA detection. With 23 tumor and 20 non-tumor clinical plasma samples, we concluded that EV-miR-486-5p and miR-21-5p are effective biomarkers for NSCLC with a small sample volumn (20-40 µL). The result was consistent to that of a commercial exosome miRNA extraction kit. These results demonstrate the effectiveness of DMF in EV pretreatment for miRNA detection, providing a facile solution to EV isolation for liquid biopsy.

Modified Gugging Swallowing Screen: A New Bedside Evaluation Tool for Swallowing Function in Patients with Open Partial Laryngectomy before Oral Feeding: A Single-Centre Retrospective Study.

BACKGROUND: Dysphagia is a prevalent complication following partial laryngectomy. We aimed to introduce a novel bedside evaluation tool, the modified Gugging Swallowing Screen (GUSS), and evaluate its reliability and validity in patients with open partial laryngectomy before oral feeding. METHODS: We conducted a retrospective analysis of 120 patients with laryngeal cancer, including 40 hospitalized patients who underwent open partial laryngectomy. On the same day before oral feeding, we performed the modified GUSS, videofluoroscopic swallowing study (VFSS), and fiberoptic endoscopic evaluation of swallowing (FEES) to evaluate swallowing function. Two independent trained nurses assessed all patients for interrater reliability of modified GUSS. We compared the results of the modified GUSS with VFSS for predictive validity, and VFSS results for solid, semisolid, and liquid intake for content validity. RESULTS: The results of VFSS and FEES showed a strong correlation and consistency (rs = 0.952, p < 0.01; κ = 0.800 to 1.000, p < 0.01). The modified GUSS exhibited substantial to excellent interrater reliability across all classification categories (rs = 0.961, p < 0.01; κ = 0.600 to 1.000, p < 0.01) and demonstrated excellent consistency and predictive validity compared to VFSS (rs = -0.931, p < 0.01; κ = 0.800 to 1.000, p < 0.01). Content validity revealed that the risk of aspiration during solid intake was lower than that during semisolid intake (p < 0.01), and the risk of aspiration during semisolid intake was lower than that during liquid intake (p < 0.01), therefore confirming the subtest sequence of the modified GUSS. CONCLUSIONS: We successfully modified GUSS for patients with open partial laryngectomy. Moreover, the new bedside screening tool was validated as an effective tool for evaluating swallowing function and the risk of aspiration in patients with open partial laryngectomy before oral feeding.

Detecting EGFR gene amplification using a fluorescence in situ hybridization platform based on digital microfluidics.

Signal transduction mediated by epidermal growth factor receptor (EGFR) gene affects the proliferation, invasion, metastasis, and angiogenesis of tumor cells. In particular, non-small cell lung cancer (NSCLC) patients with increased in copy number of EGFR gene are often sensitive to tyrosine kinase inhibitors. Despite being the standard for detecting EGFR amplification in the clinic, fluorescence in situ hybridization (FISH) traditionally involves repetitive and complex benchtop procedures that are not only time consuming but also require well-trained personnel. To address these limitations, we develop a digital microfluidics-based FISH platform (DMF-FISH) that automatically implements FISH operations. This system mainly consists of a DMF chip for reagent operation, a heating array for temperature control and a signal processing system. With the capability of automatic droplet handling and efficient temperature control, DMF-FISH performs cell digestion, gradient elution, hybridization and DAPI staining without manual intervention. In addition to operational feasibility, DMF-FISH yields comparable performance with the benchtop FISH protocol but reducing the consumption of DNA probe by 87 % when tested with cell lines and clinical samples. These results highlight unique advantages of the fully automated DMF-FISH system and thus suggest its great potential for clinical diagnosis and personalized therapy of NSCLC.

BR109, a Novel Fully Humanized T-Cell-Engaging Bispecific Antibody with GPRC5D Binding, Has Potent Antitumor Activities in Multiple Myeloma.

At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.

MOnitoring human papillomavirus Vaccine effect on Infection and cErvical diseases (MOVIE): Protocol for a cohort study using electronic health records from Yinzhou, China.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Non-invasive detection of tumor markers in salivary extracellular vesicles based on digital PCR chips.

The World Health Organization (WHO) has stated that countless cancer patients could be saved if early detection and treatment were available. However, current clinical evaluation of tumors still relies primarily on imaging examinations and tissue biopsies. These methods not only require sophisticated equipment, but also have high false positive rates or invasive problems. Here, we describe a digital polymerase chain reaction (dPCR) chip for the detection of biomarkers in salivary extracellular vesicles (SEVs), which can be used to identify markers for the early diagnosis of tumors. Based on microfluidic technology fine microstructure and microfluidics operations, this dPCR chip can accurate quantitative SEVs in a variety of tumor markers, and shows extremely strong sensitivity (10 copies). In the detection of clinical samples, the chip can effectively distinguish lung cancer cases from normal controls (P < 0.001; two-tailed t-test), and in the detection of extremely low concentration samples, it shows considerably higher precise quantitative ability than quantitative real-time polymerase chain reaction (qPCR). Overall, this study may shed new light on non-invasive early screening of tumor markers by detecting extracellular vesicle-associated markers in saliva.

Transmission grating couples and enhances the second harmonic of the electron beam to generate tunable high-power terahertz radiation.

Vacuum electronic devices utilizing free-electron-based mechanisms are a crucial class of terahertz radiation sources that operate by modulating electron beams. In this study, we introduce what we believe is a novel approach to enhance the second harmonic of electron beams and substantially increase the output power at higher frequencies. Our method employs a planar grating for fundamental modulation and a transmission grating operating in the backward region to augment the harmonic coupling. The outcome is a high power output of the second harmonic signal. Contrasting with traditional linear electron beam harmonic devices, the proposed structure can achieve an output power increase of an order of magnitude. We have investigated this configuration computationally within the G-band. Our findings indicate that an electron beam density of 50 A/cm2 at 31.5 kV can produce a 0.202 THz center frequency signal with an output power of 4.59 W. As the electron beam voltage is adjusted from 23 kV to 38.5 kV, the output signal frequency shifts from 0.195 THz to 0.205 THz, generating several watts of power output. The starting oscillation current density at the center frequency point is 28 A/cm2, which is significantly lower in the G-band compared to conventional electron devices. This reduced current density has substantial implications for the advancement of terahertz vacuum devices.

Droplet magnetic-controlled microfluidic chip integrated nucleic acid extraction and amplification for the detection of pathogens and tumor mutation sites.

Traditional nucleic acid extraction and detection is based on open operation, which may cause cross-contamination and aerosol formation. This study developed a droplet magnetic-controlled microfluidic chip integrated nucleic acid extraction, purification and amplification. The reagent is sealed in oil to form a droplet, and the nucleic acid is extracted and purified by controlling the movement of the magnetic beads (MBs) through a permanent magnet, ensuring a closed environment. This chip can automatically extract nucleic acid from multiple samples within 20 min, and can be directly placed in the in situ amplification instrument for amplification without further transfer of nucleic acid, characterized by simple, fast, time-saving and labor-saving. The results showed that the chip was able to detect <10 copies/test SARS-CoV-2 RNA, and EGFR exon 21 L858R mutations were detected in H1975 cells as low as 4 cells. In addition, on the basis of the droplet magnetic-controlled microfluidic chip, we further developed a multi-target detection chip, which used MBs to divide the nucleic acid of the sample into three parts. And the macrolides resistance mutations A2063G and A2064G, and the P1 gene of mycoplasma pneumoniae (MP) were successfully detected in clinical samples by the multi-target detection chip, providing the possibility for future application in the detection of multiple pathogens.

Metformin ameliorates ferroptosis in cardiac ischemia and reperfusion by reducing NOX4 expression via promoting AMPKα.

CONTEXT: Metformin (Met) has a protective effect against cardiac ischemia and reperfusion (I/R) injury. OBJECTIVE: This study uncovered the Met effect on ferroptosis in cardiac I/R. MATERIALS AND METHODS: Sprague-Dawley rats underwent cardiac I/R treatment (ischaemia 30 min; reperfusion 24 h) (I/R group), and administered intravenously with Met (200 mg/kg) (I/R + Met group). Haematoxylin-eosin staining, Prussian blue staining, immunohistochemistry and transmission electron microscope were conducted on cardiac tissues. H9c2 cells underwent oxygen-glucose deprivation/reoxygenation (OGD/R group) and treated by Met (0.1 mM) (OGD/R + Met group). Adenosine monophosphate-activated protein kinase α (AMPKα) siRNA was transfected into OGD/R-induced H9c2 cells. Cell counting kit-8 (CCK-8) assay, dichloro-dihydro-fluorescein diacetate (DCFH-DA) and JC-1 staining were conducted on H9c2 cells. Ferroptosis-related indicators and gene expression were detected by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: In cardiac I/R rat, Met decreased heart and serum MDA, cardiac and serum non-heme iron, and serum CK-MB and LDH (inhibition rate: 50.0%, 48.8%, 47.6%, 29.5%, 30.6% and 34.7%, respectively), relieved cardiac tissue ferroptosis and mitochondria damage, increased fraction shortening and ejection fraction (157.5% and 146.2% on day 28, respectively), up-regulated AMPKα and down-regulated NOX4 in cardiac tissues. In OGD/R-induced H9c2 cells, Met (0.1 mM) increased cell viability (promotion rate: 170.0%), decreased non-heme iron and MDA (inhibition rate: 30.1% and 47.9%, respectively), relieved ferroptosis, up-regulated AMPKα and down-regulated NOX4. AMPKα silencing abrogated these effects of Met on the OGD/R-induced H9c2 cells. DISCUSSION AND CONCLUSIONS: Met shows effectiveness in relieving ferroptosis in cardiac I/R. In the future, Met may be an effective drug for relieving ferroptosis in cardiac I/R patients clinically.

Promising efficacy of immune checkpoint inhibitor plus chemotherapy for thoracic SMARCA4-deficient undifferentiated tumor.

PURPOSE: Thoracic SMARCA4-deficient undifferentiated tumor (SD-UT) is a highly aggressive disease that is nosologically related to but distinct from SMARCA4-deficient non-small cell lung cancer (SD-NSCLC). No standard treatment guidelines were established for SD-UT. This research explored the efficacy of different treatments in SD-UT, and the prognostic, clinicopathologic and genomic difference between SD-UT and SD-NSCLC. MATERIALS AND METHODS: Information of 25 SD-UT and 22 SD-NSCLC patients diagnosed and treated in Fudan University Shanghai Cancer Center from January, 2017 to September, 2022 was analyzed. RESULTS: SD-UT was similar to SD-NSCLC in characteristics of onset age, male prevalence, heavy smoking history and metastatic pattern. SD-UT showed a rapid relapse pattern after radical therapy. For Stage IV SD-UT patients, immune checkpoint inhibitor (ICI) plus chemotherapy significantly improved median progression-free survival (PFS) compared to traditional chemotherapy as first-line treatment (26.8 vs. 2.73 months, p = 0.0437), while objective response rates of two arms were comparable (71.4% vs. 66.7%). No significant survival differences were observed between SD-UT and SD-NSCLC under similar treatment settings. SD-UT or SD-NSCLC patients receiving ICI in the first line had significantly prolonged OS than those with ICI in the latter lines or without ICI treatment throughout clinical courses. Genetic study found frequent SMARCA4, TP53 and LRP1B mutations in SD-UT. CONCLUSION: To the best of our knowledge, this is the largest series to date to compare the efficacy of ICI-based treatment to chemotherapy and document frequent mutations of LRP1B in SD-UT. ICI plus chemotherapy is an effective strategy for Stage IV SD-UT.

LncRNA LINC01094 Promotes Cells Proliferation and Metastasis through the PTEN/AKT Pathway by Targeting AZGP1 in Gastric Cancer.

Long noncoding RNAs (lncRNAs) were recently reported to play an essential role in multiple cancer types. Herein, through next-generation sequencing, we screened metastasis-driving molecules by using tissues from early-stage gastric cancer (GC) patients with lymph node metastasis, and we identified a lncRNA LINC01094, which was associated with the metastasis of GC. According to the clinical data from the TCGA, GSE15459, and GSE62254 cohorts, the high expression of LINC01094 was associated with an unfavorable prognosis. Moreover, 106 clinical GC and paired normal samples were collected, and the qRT-PCR results showed that the high expression of LINC01094 was associated with high T and N stages and a poor prognosis. We found that LINC01094 promotes the proliferation and metastasis of GC in vitro and in vivo. AZGP1 was found as the protein-binding partner of LINC01094 by using RNA pulldown and RNA-binding protein immunoprecipitation (RIP) assays. LINC01094 antagonizes the function of AZGP1, downregulates the expression of PTEN, and further upregulates the AKT pathway. Collectively, our results suggested that LINC01094 might predict the prognosis of GC patients and become the therapy target for GC.

Modulating Catalytic Activity and Stability of Atomically Precise Gold Nanoclusters as Peroxidase Mimics via Ligand Engineering.

Metal nanoclusters (NCs), composed of a metal core and protecting ligands, show promising potentials as enzyme mimics for producing fuels, pharmaceuticals, and valuable chemicals, etc. Herein, we explore the critical role of ligands in modulating the peroxidase mimic activity and stability of Au NCs. A series of Au15(SR)13 NCs with various thiolate ligands [SR = N-acetyl-l-cysteine (NAC), 3-mercaptopropionic acid (MPA), or 3-mercapto-2-methylpropanoic acid (MMPA)] are utilized as model catalysts. It is found that Au15(NAC)13 shows higher structural stability than Au15(MMPA)13 and Au15(MPA)13 against external stimuli (e.g., pH, oxidants, and temperature) because of the intramolecular hydrogen bonds. More importantly, detailed enzymatic kinetics data show that the catalytic activity of Au15(NAC)13 is about 4.3 and 2.7 times higher than the catalytic activity of Au15(MMPA)13 and Au15(MPA)13, respectively. Density functional theory (DFT) calculations reveal that the Au atoms on the motif of Au NCs should be the active centers, whereas the superior peroxidase mimic activity of Au15(NAC)13 should originate from the emptier orbitals of Au atoms because of the electron-withdrawing effect of acetyl amino group in NAC. This work demonstrates the ligand-engineered electronic structure and functionality of atomically precise metal NCs, which afford molecular and atomic level insights for artificial enzyme design.

Single-port inflatable mediastinoscopic esophagectomy is a cure for esophageal cancer patients: Case report.

RATIONALE: It is often difficult to perform transthoracic esophagectomy (TTE) in patients with chest deformities, as these patients may be lost to surgery for non-oncological reasons. PATIENT CONCERNS: In this case, we had a patient with esophageal squamous cell carcinoma (ESCC) who was not suitable for TTE because of extensive thoracic adhesions caused by the left pneumonectomy 8 years ago. DIAGNOSES: ESCC. INTERVENTIONS: Based on Professor Fujiwara's surgical method, we further improved it by proposing a single-port inflatable mediastinoscopy combined with laparoscopic-assisted esophagectomy. OUTCOMES: At the time of this writing, computed tomography and gastroscopy revealed no stenosis of anastomosis, and no evidence of disease recurrence. LESSONS: To the best of our knowledge, the present case is the first single-port inflatable mediastinoscopic esophagectomy performed on a patient undergoing pneumonectomy.

Altered Gut Microbial Profile Accompanied by Abnormal Fatty Acid Metabolism Activity Exacerbates Endometrial Cancer Progression.

Endometrial cancer (EC) is the most prevalent gynecological malignancy, with a higher risk in obese woman, indicating the possibility of gut microbiota involvement in EC progression. However, no direct evidence of a relationship between EC and gut microbiota in humans has been discovered. Here, we performed 16S rRNA sequencing to explore the relationship between dysbiosis of gut microbiota and cancer development in different types of EC patients. The results clearly show the differential profiles of gut microbiota between EC patients and normal participants as well as the association between gut microbiota and EC progression. Targeted metabolomics of plasma revealed an increased level of C16:1 and C20:2, which was positively associated with the abundance of Ruminococcus sp. N15.MGS-57. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects not only was positively associated with blood C16:1 and C20:2 but also was negatively correlated with betalain and indole alkaloid biosynthesis. Furthermore, the combined marker panel of gut bacteria, blood metabolites, and clinical indices could distinguish the EC patients under lean and overweight conditions from normal subjects with high accuracy in both discovery and validation sets. In addition, the alteration of tumor microenvironment metabolism of EC was characterized by imaging mass microscopy. Spatial visualization of fatty acids showed that C16:1 and C18:1 obviously accumulate in tumor tissue, and C16:1 may promote EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1 in EC tissues, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment. IMPORTANCE A growing number of studies have shown the connection between gut microbiota, obesity, and cancer. However, to our knowledge, the association between gut microbiota and endometrial cancer progression in humans has not been studied. We recruited EC and control individuals as research participants and further subgrouped subjects by body mass index to examine the association between gut microbiota, metabolites, and clinical indices. The higher richness of Ruminococcus sp. N15.MGS-57 in EC subjects was not only positively associated with blood C16:1 but also negatively correlated with betalain and indole alkaloid biosynthesis. Spatial visualization of fatty acids by imaging mass microscopy showed that C16:1 obviously accumulates in tumor tissue, and C16:1 may promote the EC cell invasion and metastasis through mTOR signaling. The aberrant fecal microbiome, more specifically, Ruminococcus sp. N15.MGS-57 and spatially distributed C16:1, can be used as a biomarker of clinical features and outcomes and provide a new therapeutic target for clinical treatment.

IL-2K35C-moFA, a Long-Acting Engineered Cytokine with Decreased Interleukin 2 Receptor α Binding, Improved the Cellular Selectivity Profile and Antitumor Efficacy in a Mouse Tumor Model.

Human interleukin 2 (IL-2) has shown impressive results as a therapeutic agent for cancer. However, IL-2-based cancer therapy is limited by strong Treg amplification owing to its high binding affinity to IL-2 receptor α (IL-2Rα) and its short half-life owing to its small molecular size. In this study, we solved these problems using a covalent modification strategy of the IL-2 variant, i.e., substituting cysteine (C) for lysine (K) at position 35, using octadecanedicarboxylic acid through maleimide chemistry, creating IL-2K35C-moFA. IL-2K35C-moFA was equipotent to human IL-2 wild type (IL-2WT) in activating tumor-killing CD8+ memory effector T cells (CD8+ T) and NK cells bearing the intermediate affinity IL-2 receptors, and less potent than IL-2WT on CTLL-2 cells bearing the high-affinity IL-2 receptors. Moreover, it was shown to support the preferential activation of IL-2 receptor ß (IL-2Rß) over IL-2Rα because of the mutation and fatty acid conjugation. In a B16F10 murine tumor model, IL-2K35C-moFA showed efficacy as a single dose and provided durable immunity for 1 week. Our results support the further evaluation of IL-2K35C-moFA as a novel cancer immunotherapy.