Maintenance treatment of immunotherapy after microwave ablation plus drug-eluting bead bronchial arterial chemoembolization for advanced non-small cell lung cancer: a retrospective single-center cohort study.

Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.

Severe flood modulates the sources and age of dissolved organic carbon in the Yangtze River Estuary.

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

Wettability behavior of DTMS modified SiO2: Experimental and molecular dynamics study.

In this research, the wetting behavior of SiO2 modified with dodecyltrimethoxysilane (DTMS) was explored using both experimental and molecular dynamics (MD) simulation approaches. The experimental results reveal that DTMS can chemically bond to the SiO2 surface, and the contact angle (CA) reaches the maximum value of 157.7° when the mass of DTMS is twice that of SiO2. The different wetting behaviors caused by DTMS grafting were analyzed by CA fitting, ionic pairs, concentration distribution, molecule orientation, and interfacial interaction energy. The results demonstrate that a 25 % DTMS grafting rate resulted in a maximum CA of 158.2°, which is ascribed to the disruption of interfacial hydrogen bonding and changes in the hydration structure caused by DTMS grafting. Moreover, the above hydrophobic SiO2 model shows a slight decrease in CA as the water temperature increases, which is consistent with the experimental findings. In contrast, an opposite change was observed for the pristine SiO2 model. Although the higher water temperature enhances the diffusion capacity of water molecules in both models, the difference in interfacial interactions is responsible for the change in CA. We hope this finding will contribute to a deeper understanding of the wetting adjustment of SiO2.

Achieving a Deeply Desodiated Stabilized Cathode Material by the High Entropy Strategy for Sodium-ion Batteries.

Manganese-based layered oxides are currently of significant interest as cathode materials for sodium-ion batteries due to their low toxicity and high specific capacity. However, the practical applications are impeded by sluggish intrinsic Na+ migration and poor structure stability as a result of Jahn-Teller distortion and complicated phase transition. In this study, a high-entropy strategy is proposed to enhance the high-voltage capacity and cycling stability. The designed P2-Na0.67Mn0.6Cu0.08Ni0.09Fe0.18Ti0.05O2 achieves a deeply desodiation and delivers charging capacity of 158.1 mA h g-1 corresponding to 0.61 Na with a high initial Coulombic efficiency of 98.2%. The charge compensation is attributed to the cationic and anionic redox reactions conjunctively. Moreover, the crystal structure is effectively stabilized, leading to a slight variation of lattice parameters. This research carries implications for the expedited development of low-cost, high-energy-density cathode materials for sodium-ion batteries.

Determining patient acceptable symptom states from patient reported outcome measures following reverse shoulder arthroplasty: Constant-murley, UCLA, Oxford Shoulder Scores.

Aims: To establish cut-off values for Patient-Acceptable Symptom States (PASS) in three Patient Reported Outcome Measures (PROMs), the Constant-Murley Score (CMS) and University of California Los Angeles (UCLA) Shoulder Score and Oxford Shoulder Score (OSS) at 3, 6, and 12-months following reverse shoulder arthroplasty (RSA). Methods: A retrospective study was conducted for individuals who were treated for massive rotator cuff tear, rotator cuff arthropathy or proximal humerus fractures with RSA from January 2011 and February 2020. This study included patients who have completed the patient reported outcome measures (PROMs) and satisfaction questions preoperatively, and at 3, 6 and 12-months after the procedure. Functional outcome were evaluated by CMS, UCLA shoulder score and OSS, with one anchoring question regarding satisfaction. PASS thresholds for each PROM were obtained with the Youden method, by using the receiver operating characteristic analysis, and secondary analysis was performed with the 80% specificity and 75th percentile method. Results: 129 patients were included. 74.2%, 83.9%, and 89.3% of patients were found to have a satisfactory symptom state at 3, 6 and 12-months postoperatively. At 3, 6 and 12-month intervals, the respective PASS thresholds were 42, 39 and 52 for CMS, 17, 21 and 26 for UCLA score and 28, 25 and 18 for OSS. Conclusions: PASS thresholds for RSA at 3, 6 and 12-months were found for CMS (42, 39, 52), UCLA (17, 21, 26) and OSS (28, 25, 18). These thresholds suggest increasing expectations with a trend towards higher functional requirements at each time point.

SLC2A3 promotes tumor progression through lactic acid-promoted TGF-ß signaling pathway in oral squamous cell carcinoma.

BACKGROUNDS: Oral squamous cell carcinoma is a malignant tumor of the head and neck, and its molecular mechanism remains to be explored. METHODS: By analyzing the OSCC data from the TCGA database, we found that SLC2A3 is highly expressed in OSCC patients. The expression level of SLC2A3 was verified by RT-PCR and western blotting in OSCC cell lines. The function of SLC2A3 in OSCC cell lines and Lactic acid in SLC2A3-knockdown OSCC cells were detected by colony formation, CCK8, transwell, and wound healing assays. The effect of SLC2A3 on tumor growth and metastasis was tested in vivo. GSEA and Western blot were used to analyze and validate tumor phenotypes and signaling pathway molecules. RESULTS: We analyzed OSCC datasets in the TCGA database and found that SLC2A3 had abnormally high expression and was associated with poor prognosis. We also found that oral squamous cell carcinoma cells had increased proliferation, migration, invasion, EMT phenotype, and glycolysis due to SLC2A3 overexpression. Conversely, SLC2A3 knockdown had the opposite effect. Our in vivo experiments confirmed that SLC2A3 overexpression promoted tumor growth and metastasis while knockdown inhibited it. We also observed that high SLC2A3 expression led to EMT and the activation of the TGF-ß signaling pathway, while knockdown inhibited it. Interestingly, exogenous lactic acid restored the EMT, proliferation, migration, and invasion abilities of oral cancer cells inhibited by knocking down SLC2A3. CONCLUSIONS: Our study reveals that SLC2A3 expression was up-regulated in OSCC. SLC2A3 activates the TGF-ß signaling pathway through lactic acid generated from glycolysis, thus regulating the biological behavior of OSCC.

Cannabidiol improves the cognitive function of SAMP8 AD model mice involving the microbiota-gut-brain axis.

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

Unicompartmental knee arthroplasty in obese patients, poorer survivorship at 15 years.

Introduction: The preclusion of obese patients from unicompartmental knee arthroplasty (UKA) has increasingly been challenged. This study aimed to evaluate the impact of Body Mass Index (BMI) on UKA at 15-year follow-up. Materials and methods: 169 unilateral UKA patients from 2003 to 2007 were followed-up prospectively for at least 15 years. 70 patients were left for analysis after accounting for patient demise, revision surgery and loss to follow-up. 48 of these patients (69%) were in the Control group (BMI <30 kg/m2) and 22 (31%) were in the Obese group (BMI ≥30 kg/m2). Patients were assessed before and after operation using the Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS), Oxford Knee Score (OKS), and Physical (PCS) and Mental (MCS) component of the Short Form 12. Survivorship analysis was also performed. Results: Obese patients went through UKA at an earlier age than the non-obese patients (54.7 ± 4.7 years compared to 59.9 ± 7.8 years, p = 0.005). At 2, 10, and 15-year follow-up, both groups achieved clinically significant improvements in outcomes. There was no significant association found between obesity and outcome using multiple linear regression. While propensity matching found PCS improvement at 2 years to be greater in obese patients, no significant association between obesity and 15-year outcome was found. All 13 patients who required revision, underwent total knee arthroplasty (TKA). The overall 15-year survivorship was 74.2% within the obese group and 92.4% within the control group. Conclusion: Compared to non-obese patients, obese patients had poorer 15-year survivorship with greater odds of requiring revision surgery. However, assuming implant survival, obese patients can expect a non-inferior outcome relative to their non-obese counterparts in all patient reported outcome measures 15 years after surgery.

The protective effect and mechanism of glycosides of cistanche deserticola on rats in middle cerebral artery occlusion (MCAO) model.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

Effect of total flavonoids of Dracocephalum moldavica L. On neuroinflammation in Alzheimer's disease model amyloid-ß (Aß1-42)-peptide-induced astrocyte activation.

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.

The gasdermin family: emerging therapeutic targets in diseases.

The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

A calix[3]carbazole-based cavitand: synthesis, structure and its complexation with fullerenes.

A calix[3]carbazole-based cavitand was conveniently synthesized. It was found that the cavitand with adjustable conformation could show excellent complexation with fullerenes C60 and C70 in both solution and the solid state. Moreover, the crystal structures of the host-guest complexes show that the cavitand can stack into channel-like architectures, in which fullerenes are orderly arranged inside.

Broadband beam collimation metasurface for full-color micro-LED displays.

Near-eye displays are widely recognized as a groundbreaking technological advancement with the potential to significantly impact daily life. Within the realm of near-eye displays, micro-LEDs have emerged as a highly promising technology owing to their exceptional optical performance, compact form factor, and low power consumption. However, a notable challenge in integrating micro-LEDs into near-eye displays is the efficient light collimation across a wide spectrum range. In this paper, we propose what we believe to be a novel design of a broadband beam collimation metasurface for full-color micro-LEDs by harnessing wavefront phase modulation based on Huygens' principle. Our results demonstrate a substantial reduction in the full width at half maximum (FWHM) angles, achieving a reduction to 1/10, 1/10, and 1/20 for red, green, and blue micro-LEDs compared to those without the metasurface, which is the best collimation result as far as we know. The central light intensity increases by 24.60, 36.49, and 42.15 times. Furthermore, the significant enhancement in the light energy within ±10° is achieved, with the respective multiplication factors of 14.16, 15.60, and 13.00. This metasurface has the potential to revolutionize the field by enabling high-performance, compact, and lightweight micro-LED displays, with applications in near-eye displays, micro-projectors, and beyond.

Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers.

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

microRNA-141-3p Suppressed the Progression of the Clear Cell Renal Cell Carcinoma by Targeting Transforming Growth Factor Beta 2 Gene Expression.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of kidney epithelial cells, one of the most common tumors in the world. Transforming growth factor beta (TGFß)1 is a crucial factor that induces epithelial-mesenchymal transition (EMT) in cancer cells. microRNA-141-3p (miR-141-3p) is a microRNA that is considered a tumor suppressor. However, the role and mechanism of miR-141-3p in TGFß1-induced ccRCC cells are not fully understood. This study investigated the roles of miR-141-3p and its target gene in regulating EMT in ccRCC development. 786-0 and Caki-1cells were treated with TGFß1 to induce EMT. The levels of miR-141-3p and TGFß2 were determined by quantitative real-time polymerase chain reaction and Western blotting. The progression of EMT was evaluated by E-cadherin detection by immunofluorescence, and E-cadherin, N-cadherin, and vimentin detection by Western blotting. Furthermore, migration and invasion capacities were assessed using a Transwell system. The direct binding of miR-141-3p with the target gene TGFß2 was confirmed by dual luciferase reporter gene assay. Results indicated that TGFß1 treatment decreased the protein abundance of E-cadherin while increasing the protein expression of N-cadherin and vimentin, indicating TGFß1-induced EMT was constructed successfully. Moreover, TGFß1 treatment repressed the expression of miR-141-3p. miR-141-3p mimics reversed the effect of TGFß1 on the migration, invasion, and expression of E-cadherin, N-cadherin, and vimentin. The miR-141-3p directly binds with the 3' untranslated region of TGFß2 mRNA and suppresses its expression. Furthermore, TGFß2 overexpression abrogated the above changes regulated by miR-141-3p mimics. Taken together, miR-141-3p inhibited TGFß1-induced EMT by suppressing the migration and invasion of ccRCC cells via directly targeting TGFß2 gene expression.

The Impact of China's Family Floating Population on the Participation of Medical Insurance in the Inflow Areas.

Background: With the transformation of China's economy and society, the floating population has also shown a new development trend, from individual migration to co-migration with family members. In 2020, among the 376 million floating population, the population flowing to cities and towns was 330 million, accounting for nearly 88.1%. The family mobility of the floating population is not just a simple personal gathering or geographical migration, but a profound adjustment of the living environment, social interaction and the interests of family members. Migrants no longer simply play the role of " urban passers-by", but gradually move with spouses, children, parents, and even settle in the city, which will inevitably produce different public service and social security needs. Objective: To explore the impact of floating population's familyization on the participation of medical insurance in the inflow areas. Methods: This study adopted the form of non-systematic literature review. The key words were floating population and medical insurance. The related analysis of PubMed, Embase, CNKI, Wanfang, and VIP databases were reviewed and summarized. Results: Due to the flow between domestic immigrants and regions, their medical insurance is difficult to be guaranteed. The domestic floating population's demand for health services is increasing, but the coverage of medical services provided by medical insurance is not comprehensive enough. Conclusion: It is necessary to integrate the medical insurance system and improve the adaptability of medical insurance to family mobility; protect the welfare needs of migrant families and increase their willingness to participate in medical insurance at the destination; pay attention to the interaction and integration of floating population families, understand and guide them to participate in the status quo of medical insurance, and improve the status quo.

Real-time analysis of large-scale neuronal imaging enables closed-loop investigation of neural dynamics.

Large-scale imaging of neuronal activities is crucial for understanding brain functions. However, it is challenging to analyze large-scale imaging data in real time, preventing closed-loop investigation of neural circuitry. Here we develop a real-time analysis system with a field programmable gate array-graphics processing unit design for an up to 500-megabyte-per-second image stream. Adapted to whole-brain imaging of awake larval zebrafish, the system timely extracts activity from up to 100,000 neurons and enables closed-loop perturbations of neural dynamics.

METTL3 as a novel diagnosis and treatment biomarker and its association with glycolysis, cuproptosis and ceRNA in oesophageal carcinoma.

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.

Engineering RuBisCO-based shunt for improved cadaverine production in Escherichia coli.

The process of biological fermentation is often accompanied by the release of CO2, resulting in low yield and environmental pollution. Refixing CO2 to the product synthesis pathway is an attractive approach to improve the product yield. Cadaverine is an important diamine used for the synthesis of bio-based polyurethane or polyamide. Here, aiming to increase its final production, a RuBisCO-based shunt consisting of the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and phosphoribulate kinase (PRK) was expressed in cadaverine-producing E. coli. This shunt was calculated capable of increasing the maximum theoretical cadaverine yield based on flux model analysis. When a functional RuBisCO-based shunt was established and optimized in E. coli, the cadaverine production and yield of the final engineered strain reached the highest level, which were 84.1 g/L and 0.37 g/g Glucose, respectively. Thus, the design of in situ CO2 fixation provides a green and efficient industrial production process.