Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Lunar Regolith Geopolymer Concrete for In-Situ Construction of Lunar Bases: A Review.

The construction of lunar bases represents a fundamental challenge for deep space exploration, lunar research, and the exploitation of lunar resources. In-situ resource utilization (ISRU) technology constitutes a pivotal tool for constructing lunar bases. Using lunar regolith to create geopolymers as construction materials offers multiple advantages as an ISRU technique. This paper discusses the principle of geopolymer for lunar regolith, focusing on the reaction principle of geopolymer. It also analyzes the applicability of geopolymer under the effects of the lunar surface environment and the differences between the highland and mare lunar regolith. This paper summarizes the characteristics of existing lunar regolith simulants and the research on the mechanical properties of lunar regolith geopolymers using lunar regolith simulants. Highland lunar regolith samples contain approximately 36% amorphous substances, the content of silicon is approximately 28%, and the ratios of Si/Al and Si/Ca are approximately 1.5 and 2.6, respectively. They are more suitable as precursor materials for geopolymers than mare samples. The compressive strength of lunar regolith geopolymer is mainly in the range of 18~30 MPa. Sodium silicate is the most commonly utilized activator for lunar regolith geopolymers; alkalinity in the range of 7% to 10% and modulus in the range of 0.8 to 2.0 are suitable. A vacuum environment and multiple temperature cycles reduce the mechanical properties of geopolymers by 8% to 70%. Future research should be concentrated on the precision control of the lunar regolith's chemical properties and the alkali activation efficacy of geopolymers in the lunar environment.

Femtosecond laser 3D printed micro objective lens for ultrathin fiber endoscope.

The most important optical component in an optical fiber endoscope is its objective lens. To achieve a high imaging performance level, the development of an ultra-compact objective lens is thus the key to an ultra-thin optical fiber endoscope. In this work, we use femtosecond laser 3D printing to develop a series of micro objective lenses with different optical designs. The imaging resolution and field-of-view performances of these printed micro objective lenses are investigated via both simulations and experiments. For the first time, multiple micro objective lenses with different fields of view are printed on the end face of a single imaging optical fiber, thus realizing the perfect integration of an optical fiber and objective lenses. This work demonstrates the considerable potential of femtosecond laser 3D printing in the fabrication of micro-optical systems and provides a reliable solution for the development of an ultrathin fiber endoscope.

Folic acid protects against isoniazid-induced liver injury via the m6A RNA methylation of cytochrome P450 2E1 in mice.

Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury. Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism. Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1. Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.

Chemoselective Synthesis of α-Halo-α,α-difluoromethyl Ketones from Trimethyl(phenylethynyl)silane.

Here, we describe a novel strategy for chemoselective synthesis of α-halo-α,α-difluoromethyl ketones (-COCF3 and -COClCF2 motifs) from trimethyl(phenylethynyl)silane under catalyst-free and mild conditions. Commercially available Selectfluor or additional NaCl as halogen reagent was employed to complete this transformation, thereby demonstrating the potential synthetic value of this new reaction in organic synthesis.

The ratio of circulating CD56dim NK cells to follicular T helper cells as a promising predictor for disease activity of relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system primarily mediated by CD4+ T helper cells. This study investigated the dynamic changes of natural killer (NK) cells and follicular T helper (Tfh) cells and their associations in relapsing-remitting MS patients. The findings revealed inverse relationships between NK cells and CD4+ T cells or Tfh cells. Specifically, CD56dim NK cells, not CD56bright NK cells, were negatively correlated with CD4+ T cells and Tfh cells. However, no significant correlations were found between NK cells and sNfL levels or EDSS scores. The ratio of CD56dim NK cells to circulating Tfh (cTfh) cells demonstrated superior discriminatory ability in distinguishing relapsing MS patients from healthy controls (HCs) and remitting patients, as determined by receiver operating characteristic (ROC) analysis. Following treatment with immunosuppressants or disease-modifying therapies (DMTs), a significant increase in the CD56dim NK/cTfh ratio was observed. These findings suggest that the CD56dim NK/cTfh ratio holds promise as a prognostic indicator for clinical relapse and treatment response in MS.

Shuangdong Capsule Activates Insulin Signal Pathway to Improve Urinary Tract Infection in Diabetic Rats.

BACKGROUND AND AIM: Diabetes and Urinary Tract Infections (UTIs) are both common and serious health problems. Shuangdong capsule, a Chinese patent medicine, has been used to treat these conditions. This study assesses its efficacy and mechanism in treating diabetes combined with UTIs. METHODS: We induced diabetes in rats using streptozotocin and UTIs with Escherichia coli, dividing the rats into five groups: control, model, levofloxacin, Shuangdong capsule, and levofloxacin + Shuangdong capsule. After two weeks, we measured blood glucose, insulin, infection indicators, and bladder histology. We also detected the expression of insulin receptor substrate 1 (IRS1)-phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-C-X-C motif chemokine ligand 2 (CXCL2) signaling pathway by Western Blot and the myeloperoxidase (MPO) levels by Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, we conducted a Mendelian randomization study using genetic variants of the insulin receptor to assess its causal effect on UTI risk. RESULTS: Shuangdong capsule improved bladder pathology and infection indicators, similar to levofloxacin. It did not affect blood glucose or insulin levels. Moreover, it reversed the suppression of the IRS1-PI3K-Akt-CXCL2 pathway and MPO levels caused by UTI in diabetic rats. The Mendelian randomization study showed that increased insulin receptor expression reduced UTI risk, which was consistent with the results of the animal experiments. CONCLUSION: The Shuangdong capsule was effective in treating diabetes with UTIs. It may function by activating the IRS1-PI3K-Akt signaling pathway, thereby increasing CXCL2 and MPO levels, enhancing innate immunity, and promoting bacterial clearance. The Mendelian randomization study provided further evidence supporting the causal role of the insulin receptor in UTI prevention.

Understanding Emergent Complexity from a Single-Molecule Perspective.

Molecules, with structural, scaling, and interaction diversities, are crucial for the emergence of complex behaviors. Interactions are essential prerequisites for complex systems to exhibit emergent properties that surpass the sum of individual component characteristics. Tracing the origin of complex molecular behaviors from interactions is critical to understanding ensemble emergence, and requires insights at the single-molecule level. Electrical signals from single-molecule junctions enable the observation of individual molecular behaviors, as well as intramolecular and intermolecular interactions. This technique provides a foundation for bottom-up explorations of emergent complexity. This Perspective highlights investigations of various interactions via single-molecule junctions, including intramolecular orbital and weak intermolecular interactions and interactions in chemical reactions. It also provides potential directions for future single-molecule junctions in complex system research.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

From genomic insights to clinical hope: Targeting NEU1 in IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgAN), the primary form of glomerulonephritis, presents significant clinical challenges due to its obscure pathogenesis and lack of targeted treatments. We conducted a proteome-wide Mendelian randomization (MR) study to identify therapeutic targets for IgAN. METHODS: Utilizing a plasma proteome dataset comprising 4907 blood plasma proteins as the exposure variable, and renal biopsy-confirmed IgAN cases as the outcome, this study employed MR to pinpoint proteins potentially pathogenic to IgAN. The robustness of our findings was affirmed through external dataset validation, reverse causation testing, and Bayesian colocalization analysis. Additionally, we conducted phenotypic scanning and analyzed downstream metabolites to investigate candidate proteins's biological function. RESULTS: In our study, a significant association was identified between an increase in neuraminidase 1 (NEU1) expression and the risk of IgAN. Specifically, a one standard deviation increase in NEU1 expression was associated with an odds ratio of 11.80 for the development of IgAN (95% confidence interval: 4.03-34.54). This association was substantiated across various statistical models and external validations. Colocalization analysis indicated a shared causal variant between NEU1 expression and IgAN. Furthermore, an increased influenza risk associated with NEU1 was observed, supporting the therapeutic potential of NEU1 inhibitors for IgAN. However, our study found no significant role for neuraminic acid-related metabolites in IgAN's development, suggesting an independent pathway for NEU1's influence. CONCLUSION: This study identifies NEU1 as a promising therapeutic target for IgAN, backed by robust genetic evidence. Future research should explore NEU1's therapeutic potential in diverse populations and clinical scenarios, further establishing its role in IgAN.

The Natural Product Secoemestrin C Inhibits Colorectal Cancer Stem Cells via p38-S100A8 Feed-Forward Regulatory Loop.

Cancer stem cells (CSCs) are closely associated with tumor initiation, metastasis, chemoresistance, and recurrence, which represent some of the primary obstacles to cancer treatment. Targeting CSCs has become an important therapeutic approach to cancer care. Secoemestrin C (Sec C) is a natural compound with strong anti-tumor activity and low toxicity. Here, we report that Sec C effectively inhibited colorectal CSCs and non-CSCs concurrently, mainly by inhibiting proliferation, self-renewal, metastasis, and drug resistance. Mechanistically, RNA-seq analysis showed that the pro-inflammation pathway of the IL17 axis was enriched, and its effector S100A8 was dramatically decreased in Sec C-treated cells, whose roles in the stemness of CSCs have not been fully clarified. We found that the overexpression of S100A8 hindered the anti-CSCs effect of Sec C, and S100A8 deficiency attenuated the stemness traits of CSCs to enhance the Sec C killing activity on them. Meanwhile, the p38 signal pathway, belonging to the IL17 downstream axis, can also mediate CSCs and counter with Sec C. Notably, we found that S100A8 upregulation increased the p38 protein level, and p38, in turn, promoted S100A8 expression. This indicated that p38 may have a mutual feedback loop with S100A8. Our study discovered that Sec C was a powerful anti-colorectal CSC agent, and that the positive feedback loop of p38-S100A8 mediated Sec C activity. This showed that Sec C could act as a promising clinical candidate in colorectal cancer treatment, and S100A8 could be a prospective drug target.

Fortified Dual-Spectral Overlap with Enhanced Colorimetric/Fluorescence Dual-Response Immunochromatography for On-Site Bimodal-Type Gentamicin Monitoring.

Immunochromatography (ICA) remains untapped toward enhanced sensitivity and applicability for fulfilling the nuts and bolts of on-site food safety surveillance. Herein, we report a fortified dual-spectral overlap with enhanced colorimetric/fluorescence dual-response ICA for on-site bimodal-type gentamicin (Gen) monitoring by employing polydopamine (PDA)-coated AuNPs (APDA) simultaneously serving as a colorimetric reporter and a fluorescence quencher. Availing of the enhanced colorimetric response that originated from the PDA layer, the resultant APDA exhibits less required antibody and immunoprobes in a single immunoassay, which facilitates improved antibody utilization efficiency and immuno-recognition in APDA-ICA. Further integrated with the advantageous features of fortified excitation and emission dual-spectral overlap for the Arg/ATT-AuNCs, this APDA-ICA with a "turn on/off" pattern achieves the visual limits of detection of 1.0 and 0.5 ng mL-1 for colorimetric and fluorescence patterns (25- and 50-fold lower than standard AuNPs-ICA). Moreover, the excellent self-calibration and satisfactory recovery of 79.03-118.04% were shown in the on-site visual colorimetric-fluorescence analysis for Gen in real environmental media (including real river water, an urban aquaculture water body, an aquatic product, and an animal byproduct). This work provides the feasibility of exploiting fortified dual-spectral overlap with an enhanced colorimetric/fluorescence dual response for safeguarding food safety and public health.

Precise Spectral Overlap-Based Donor-Acceptor Pair for a Sensitive Traffic Light-Typed Bimodal Multiplexed Lateral Flow Immunoassay.

Bimodal-type multiplexed immunoassays with complementary mode-based correlation analysis are gaining increasing attention for enhancing the practicability of the lateral flow immunoassay (LFIA). Nonetheless, the restriction in visually indistinguishable multitargets induced by a single fluorescent color and difficulty in single acceptor ineffectual fluorescence quenching due to the various spectra of multiple different donors impede the further execution of colorimetric-fluorescence bimodal-type multiplexed LFIAs. Herein, the precise spectral overlap-based donor-acceptor pair construction strategy is proposed by regulating the size of the nanocore, coating it with an appropriate nanoshell, and selecting a suitable fluorescence donor with distinct colors. By in situ coating Prussian blue nanoparticles (PBNPs) on AuNPs with a tunable size and absorption spectrum, the resultant APNPs demonstrate efficient fluorescence quenching ability, higher colloidal stability, remarkable colorimetric intensity, and an enhanced antibody coupling efficiency, all of which facilitate highly sensitive bimodal-type LFIA analysis. Following integration with competitive-type immunoreaction, this precise spectral overlap-supported spatial separation traffic light-typed colorimetric-fluorescence dual-response assay (coined as the STCFD assay) with the limits of detection of 0.013 and 0.152 ng mL-1 for ractopamine and clenbuterol, respectively, was proposed. This work illustrates the superiority of the rational design of a precise spectral overlap-based donor-acceptor pair, hinting at the enormous potential of the STCFD assay in the point-of-care field.

Unveiling the Properties of Sulfhydryl Groups in a Single-Molecule Junction.

The metal-thiol interface is ubiquitous in nanotechnology and surface chemistry. It is not only used to construct nanocomposites but also plays a decisive role in the properties of these materials. When organothiol molecules bind to the gold surface, there is still controversy over whether sulfhydryl groups can form disulfide bonds and whether these disulfide bonds can remain stable on the gold surface. Here, we investigate the intrinsic properties of sulfhydryl groups on the gold surface at the single-molecule level using a scanning tunneling microscope break junction technique. Our findings indicate that sulfhydryl groups can react with each other to form disulfide bonds on the gold surface, and the electric field can promote the sulfhydryl coupling reaction. In addition to these findings, ultraviolet irradiation is used to effectively regulate the coupling between sulfhydryl groups, leading to the formation and cleavage of disulfide bonds. These results unveil the intrinsic properties of sulfhydryl groups on the gold surface, therefore facilitating the accurate construction of broad nanocomposites with the desired functionalities.

Hybrid Interface Chemistry Enabling Mixed Conducting via Ultrafast Microwave Polarization Toward Dendrite-Free Zn Anodes.

Zn metal anodes in aqueous electrolytes suffer from interface issues including uncontrolled dendrite growth and undesired side reactions, resulting in their limited application in terms of short circuits and cell failure. Herein, a hybrid interface chemistry strategy is developed through ultrafast microwave polarization at the skin region of bare Zn. Owing to efficient Joule heating directed by abundant local hot spots at electron valleys, the rapid establishment of a dense interfacial layer can be realized within a minute. Stabilized Zn with suppressed side reactions or surface corrosion is therefore achieved due to the interfacial protection. Importantly, hybrid zincophilic sites involving laterally/vertically interconnected Cu-Zn intermetallic compound and Zn2+ -conductive oxide species ensure mixed charge conducting (denoted as CuHL@Zn), featuring uniformly distributed electric field and boosted Zn2+ diffusion kinetics. As a consequence, CuHL@Zn in symmetric cells affords lifespans of 2800 and 3200 h with ultra-low polarization voltages (≈19 and 56 mV) at a plating capacity of 1.0 mAh cm-2 for 1 and 5 mA cm-2 , respectively. The CuHL@Zn||MnO2 full cell further exhibits cycling stability with a capacity retention of over 80% for 500 cycles at 2 A g-1 .

AI-assisted mass spectrometry imaging with in situ image segmentation for subcellular metabolomics analysis.

Subcellular metabolomics analysis is crucial for understanding intracellular heterogeneity and accurate drug-cell interactions. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieving this goal. To address this challenge, we propose an artificial intelligence-assisted subcellular mass spectrometry imaging (AI-SMSI) strategy with in situ image segmentation. Based on the nanometer-resolution MSI technique, the protonated guanine and threonine ions were respectively employed as the nucleus and cytoplasmic markers to complete image segmentation at the subcellular level, avoiding mutual interference of signals from various compartments in the cell. With advanced AI models, the metabolites within the different regions could be further integrated and profiled. Through this method, we decrypted the distinct action mechanism of isomeric drugs, doxorubicin (DOX) and epirubicin (EPI), only with a stereochemical inversion at C-4'. Within the cytoplasmic region, fifteen specific metabolites were discovered as biomarkers for distinguishing the drug action difference between DOX and EPI. Moreover, we identified that the downregulations of glutamate and aspartate in the malate-aspartate shuttle pathway may contribute to the higher paratoxicity of DOX. Our current AI-SMSI approach has promising applications for subcellular metabolomics analysis and thus opens new opportunities to further explore drug-cell specific interactions for the long-term pursuit of precision medicine.

Relationship between Serum Indoxyl Sulfate and Klotho Protein and Vascular Calcification in Patients with Chronic Kidney Disease Stages 3-5.

Objective: This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3-5. Methods: From December 2021 to January 2023, a total of 108 CKD patients in stages 3-5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results: With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0.05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0.05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0.05). Conclusion: This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification.

Correlation between gout and dry eye disease.

BACKGROUND: Gout is a common form of inflammatory arthritis that can cause a number of serious complications. Complications are common in patients with gout and complicate their management and disease outcome. The recent literature has reported that an increasing number of gout patients are presenting with dry eye symptoms. However, until now, the link between gout and dry eye disease has not been clearly defined. (It is unclear whether the two conditions simply co-exist, whether there are common risk factors, or whether dry eye disease is a complication of gout.) METHODS: A thorough literature search was conducted in the PubMed database to summarize the most recent information on the correlation between gout and dry eye disease and to explore the potential relationship between the pathogenesis of the two. (Objective: Therefore, in this paper, we review the recent literature on the correlation between gout and dry eye disease and explore the potential association between the pathogenesis of both.) RESULTS: Studies in the last five years have shown a correlation between gout and dry eye, i.e., gout is associated with an increased risk of dry eye. The NLRP3-IL-1ß signaling pathway may be a potential mechanism for the combination of gout and dry eye disease; factors such as high blood uric acid and xanthine oxidase activation in gout patients may aggravate the development of dry eye disease; reducing the use of visual display terminals; reducing or abstaining from alcohol consumption; and moderate coffee intake may effectively prevent gout and dry eye disease. CONCLUSIONS: It is an undisputed fact that many gout patients present with dry eye manifestations that seriously affect the quality of life of gout patients, and early detection and treatment of dry eye in gout patients are crucial.

An actor-critic framework based on deep reinforcement learning for addressing flexible job shop scheduling problems.

With the rise of Industry 4.0, manufacturing is shifting towards customization and flexibility, presenting new challenges to meet rapidly evolving market and customer needs. To address these challenges, this paper suggests a novel approach to address flexible job shop scheduling problems (FJSPs) through reinforcement learning (RL). This method utilizes an actor-critic architecture that merges value-based and policy-based approaches. The actor generates deterministic policies, while the critic evaluates policies and guides the actor to achieve the most optimal policy. To construct the Markov decision process, a comprehensive feature set was utilized to accurately represent the system's state, and eight sets of actions were designed, inspired by traditional scheduling rules. The formulation of rewards indirectly measures the effectiveness of actions, promoting strategies that minimize job completion times and enhance adherence to scheduling constraints. The experimental evaluation conducted a thorough assessment of the proposed reinforcement learning framework through simulations on standard FJSP benchmarks, comparing the proposed method against several well-known heuristic scheduling rules, related RL algorithms and intelligent algorithms. The results indicate that the proposed method consistently outperforms traditional approaches and exhibits exceptional adaptability and efficiency, particularly in large-scale datasets.