Synergetic sludge conditioning by US enhanced Fe2+ activated sodium persulfate: Physicochemical properties and mechanisms.

Efficient dewatering of sewage sludge is an energy- and carbon-saving procedure for sludge treatment in wastewater treatment facilities. The ultrasound-coupled divalent iron ion activated persulfate process can effectively promote sludge dewatering and improve organic substance content. Under the action of ultrasound (US 50 w/L), divalent iron ions (Fe2+) 200 mg/g (TS), and persulfate (PDS) 200 mg/g (TS) for 60 min, the capillary suction time (CST) was reduced by 79.74%, and the moisture content of the dewatered sludge cake reached 56.51 wt%. The organic carbon content of treated sludge was also four times higher than the original sludge and types were richer in short-chain volatile species in US/Fe2+/PDS. Moreover, the correlation analysis found that the relationship of between CST and SV30, Zeta and lactate dehydrogenase (LDH) were positive correlation, and the relationship of SCOD and TC were positively correlated with the PN (SB-EPS). Mechanistic studies showed that the US/Fe2+/PDS system could produce oxygen activators by US coupling Fe2+ to strengthen the effect of activated PDS strongly, while the sulfate radicals (SO4·-) radical was a dominant role. The cracking mechanism is divided into two pathways effectively degraded the macromolecule EPS into a small-molecule acid and further reduced the water-holding interfacial affinity as follow: (1) the radical path dominated by hydroxyl radicals (·OH), SO4·-, and superoxide radical (O2·-); (2) the non-radicals dominated by monoclinic oxygen (1O2). Afterwards, the electrostatic force and interfacial free energy were reduced, resulting in enhanced self-flocculation and mobility to enhanced dewaterability. These findings demonstrated the US/Fe2+/PDS system had significant advantages in sludge cracking and provided theoretical support for its practical application.

Simulation method for multi-source information fusion space target.

Current space target simulation systems suffer from limitations, such as a single simulated spectral band, inability to allocate spectral ratios between bands, and poor imaging quality of multi-spectral simulated images. We propose a multi-source information fusion spatial target simulation method system that features a "series-parallel" hybrid connection. We optimize the design of a multi-spectral common aperture optical system and experimentally verify the proposed method. The experimental results show that the proposed system can simulate a wide range of spectral bands ranging from ultraviolet to long-wave infrared. Furthermore, it achieves precise control over the ratio of simulated radiant energy among spectral bands, with a spectral simulation error of less than 4.8%. Notably, it effectively images stars against the cosmic background and spacecraft across different spectral bands. This system serves as a theoretical cornerstone and provides crucial technological support for performance testing and rapid iterative development of multi-source information fusion space exploration systems.

Natural products with potential hypoglycemic activity in T2DM: 2019-2023.

As currently the most common metabolic disease, type 2 diabetes mellitus (T2DM) has shown a continuous increase in the number of patients in recent decades. Most anti-T2DM drugs tend to cause some side effects. Given the pathogenesis of T2DM, natural products have emerged as an important source of anti-T2DM drugs. This article reviews natural products with potential hypoglycemic activity from 2019 to 2023. A total of 200 previously natural products were discovered on SciFinder, PubMed and Web of Science. These products were categorized based on their structural frameworks and their biological activities were summarized. Although the mechanisms of action of most compounds are unclear, these compounds could still serve as candidates for the development of lead compounds. Therefore, further structure and activity research of natural products will significantly contribute to the development of potential anti-T2DM drugs.

Design and analysis of unequal aperture off-axis optical integrator for solar simulators.

The unequal aperture off-axis optical integrator design method is proposed to improve the irradiation uniformity of solar simulators and solve the problem of limited uniformity of optical integrator due to aberrations and uneven distribution of incident radiation. Firstly, the unequal aperture off-axis optical integrator structure is designed based on the scalar diffraction theory to analyze the factors affecting the optical homogenization ability of the optical integrator. Then, the relationship between sub-eye lens aperture and arrangement is explored in combination with Lagrange invariance principle and semi-definite programming theory. Finally, the optimum off-axis amount of sub-eye lens with different ring band is determined from the perspective of geometric optics by using the aberration theory and following the principle of edge light, so as to improve the evenness of optical integrator. The design results are verified by the simulation analysis. The simulation results show that: In the picture plane of optical integrator, the irradiation non-uniformity in the ф 26 mm irradiation plane is 14.87%, which is better than 26.02% in the traditional optical integrator. At the same time, at the effective irradiated surface, the irradiation non-uniformity of 0.53% within the ф 300 mm reaches the irradiation standard of the class A + solar simulator, and the irradiance only decreases by 16.5% compared with the traditional optical integrator, which still meets the index requirement of a solar constant. The goal of improving the evenness of optical integrator is realized without greatly affecting irradiance and without introducing aspherical design.

Gastric metastasis from breast cancer: five cases and a single-institutional review.

Gastric metastasis from breast cancer has a high rate of misdiagnosis and missed diagnosis. Data of patients who had gastric metastasis from breast cancer were retrieved from our hospital between 2014 and 2020. The gastric metastasis from breast cancer incidence was 0.04% (5/14,169 cases of breast cancer). Four patients had invasive lobular carcinoma, and the other patient had invasive ductal carcinoma. The time from the initial diagnosis of breast cancer to the appearance of gastric metastasis ranged from 0 to 12 years. One patient's endoscopic presentation was similar to mucosal-associated lymphoid tissue lymphoma and presented with gastric mucosal congestion and edema, widened wrinkles, mixed color fading, and redness. The initial pathological diagnosis of this patient was mucosal-associated lymphoid tissue lymphoma, and breast cancer was finally confirmed by immunohistochemistry. Hormonal receptors were highly expressed in four patients with primary and metastasis lesions and were negative in one patient. Human epidermal growth factor receptor 2 was negative in all patients. Mammaglobin and GATA3 were positive in all patients. In conclusion, the gastric metastasis of breast cancer incidence rate is low, and misdiagnosis can lead to insufficient or excessive treatment. Multiple biopsies and immunohistochemistry should be performed to diagnose gastric metastasis of breast cancer.

A long noncoding RNA functions in pumpkin fruit development through S-adenosyl-L-methionine synthetase.

Long noncoding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory roles of lncRNAs underlying fruit development have not been extensively studied. The pumpkin (Cucurbita spp.) is a preferred model for understanding the molecular mechanisms regulating fruit development because of its variable shape and size and large inferior ovary. Here, we performed strand-specific transcriptome sequencing on pumpkin (Cucurbita maxima "Rimu") fruits at 6 developmental stages and identified 5,425 reliably expressed lncRNAs. Among the 332 lncRNAs that were differentially expressed during fruit development, the lncRNA MSTRG.44863.1 was identified as a negative regulator of pumpkin fruit development. MSTRG.44863.1 showed a relatively high expression level and an obvious period-specific expression pattern. Transient overexpression and silencing of MSTRG.44863.1 significantly increased and decreased the content of 1-aminocyclopropane carboxylic acid (a precursor of ethylene) and ethylene production, respectively. RNA pull-down and microscale thermophoresis assays further revealed that MSTRG.44863.1 can interact with S-adenosyl-L-methionine synthetase (SAMS), an enzyme in the ethylene synthesis pathway. Considering that ethylene negatively regulates fruit development, these results indicate that MSTRG.44863.1 plays an important role in the regulation of pumpkin fruit development, possibly through interacting with SAMS and affecting ethylene synthesis. Overall, our findings provide a rich resource for further study of fruit-related lncRNAs while offering insights into the regulation of fruit development in plants.

High contrast ratio optimized total internal reflection prism for compact medium-wave IR target simulation system.

The existing infrared target simulation system with a total internal reflection (TIR) prism has the problem of low imaging contrast ratio, which will seriously affect the quality of the simulated image. This study proposes a design method of optimized TIR prism (OTIR) based on Snell's law in medium-wave infrared (MWIR) to solve the problem. The radiation theory is used to construct the constraint model of the OTIR prism in the MWIR target simulation system. Further, this study investigates the influence of different states of the digital micromirror device on the beam direction and derives the design equation of the OTIR prism composed of three prisms based on Snell's law. Finally, the designed OTIR prism is simulated and experimentally verified. The simulated results show that the OTIR prism of the compact MWIR target simulation system can enhance the contrast ratio. The experimental results show that the output contrast ratio of the simulation system at 700 K is about 298:1. In the specified temperature range, the contrast ratio of the infrared target simulation system increases with the increase of the light source temperature. Thus, the OTIR prism has the function of improving the contrast ratio of MWIR target simulation system.

Design, Synthesis, and Antitumor Activity Evaluation of Novel VISTA Small Molecule Inhibitors.

VISTA (V-domain Ig suppressor of T cell activation) is a novel immune checkpoint protein and represents a promising target for cancer immunotherapy. Here, we report the design, synthesis, and evaluation of a series of methoxy-pyrimidine-based VISTA small molecule inhibitors with potent antitumor activity. By employing molecular docking and microscale thermophoresis (MST) assay, we identified a lead compound A1 that binds to VISTA protein with high affinity and optimized its structure. A4 was then obtained, which exhibited the strongest binding ability to VISTA protein, with a KD value of 0.49 ± 0.20 µM. In vitro, A4 significantly activated peripheral blood mononuclear cells (PBMCs) induced the release of cytokines such as IFN-γ and enhanced the cytotoxicity of PBMCs against tumor cells. In vivo, A4 displayed potent antitumor activity and synergized with PD-L1 antibody to enhance the therapeutic effect against cancer. These results suggest that compound A4 is an effective VISTA small molecule inhibitor, providing a basis for the future development of VISTA-targeted drugs.

The value of CT shape quantification in predicting pathological classification of lung adenocarcinoma.

OBJECTIVE: To evaluate whether quantification of lung GGN shape is useful in predicting pathological categorization of lung adenocarcinoma and guiding the clinic. METHODS: 98 patients with primary lung adenocarcinoma were pathologically confirmed and CT was performed preoperatively, and all lesions were pathologically ≤ 30 mm in size. On CT images, we measured the maximum area of the lesion's cross-section (MA). The longest diameter of the tumor (LD) was marked with points A and B, and the perpendicular diameter (PD) was marked with points C and D, which was the longest diameter perpendicular to AB. and D, which was the longest diameter perpendicular to AB. We took angles A and B as big angle A (BiA) and small angle A (SmA). We measured the MA, LD, and PD, and for analysis we derived the LD/PD ratio and the BiA/SmA ratio. The data were analysed using the chi-square test, t-test, ROC analysis, and binary logistic regression analysis. RESULTS: Precursor glandular lesions (PGL) and microinvasive adenocarcinoma (MIA) were distinguished from invasive adenocarcinoma (IAC) by the BiA/SmA ratio and LD, two independent factors (p = 0.007, p = 0.018). Lung adenocarcinoma pathological categorization was indicated by the BiA/SmA ratio of 1.35 and the LD of 11.56 mm with sensitivity of 81.36% and 71.79%, respectively; specificity of 71.79% and 74.36%, respectively; and AUC of 0.8357 (95% CI: 0.7558-0.9157, p < 0.001), 0.8666 (95% CI: 0.7866-0.9465, p < 0.001), respectively. In predicting the pathological categorization of lung adenocarcinoma, the area under the ROC curve of the BiA/SmA ratio combined with LD was 0.9231 (95% CI: 0.8700-0.9762, p < 0.001), with a sensitivity of 81.36% and a specificity of 89.74%. CONCLUSIONS: Quantification of lung GGN morphology by the BiA/SmA ratio combined with LD could be helpful in predicting pathological classification of lung adenocarcinoma.

Distinctive species interaction patterns under high nitrite stress shape inefficient denitrifying phosphorus removal performance.

Denitrifying phosphorus removal using nitrite as an electron acceptor is an innovative, resource-efficient approach for nitrogen and phosphorus removal. However, the inhibitory effects of nitrite on anoxic phosphorus uptake and process stability are unclear. This study investigated the total phosphorus removal performance under nitrite stress and analyzed microbiome responses in 186 sludge samples. The results indicated that the total phosphorus removal rates and dominant taxon abundance were highly similar under nitrite stress. High nitrite stress induced a community-state shift, leading to unstable dynamics and decreased total phosphorus removal. This shift resulted from increased species cooperation. Notably, the shared genera OLB8 and Zoogloea under non-inhibitory nitrite stress, suggesting their vital roles in mitigating nitrite stress by enhancing carbon and energy metabolism. The response patterns of these bacterial communities to high nitrite stress can guide the design and optimization of high-nitrogen wastewater reactors.

Proteomic Analysis of Frozen-Thawed Spermatozoa with Different Levels of Freezability in Dairy Goats.

The results of artificial insemination (AI) are adversely affected by changes in sperm motility and function throughout the cryopreservation procedure. The proteome alterations of frozen-thawed spermatozoa with various levels of freezability in dairy goats, however, remain largely unknown. To discover differentially expressed proteins (DEPs) and their roles in dairy goat sperm with high or low freezability (HF or LF), we conducted 4D-DIA quantitative proteomics analysis, the results of which are presented in this work. Additionally, we explored the underlying processes that may lead to the variations in sperm freezing resistance. A total of 263 DEPs (Fold Change > 2.0, p-value < 0.05) were identified between the HF group and LF group in frozen-thawed dairy goat spermatozoa. In our Gene Ontology (GO) enrichment analysis, the DEPs were mostly associated with the regulation of biological processes, metabolic processes, and responses to stress and cellular component biogenesis. Our Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis also revealed that the DEPs were predominantly engaged in oxidative phosphorylation, N-Glycan biosythesis, and cysteine and methionien metabolism. A protein-protein interaction (PPI) network analysis revealed 14 potential proteins (NUDFB8, SDHC, PDIA4, HSPB1, etc.) that might influence the freezability of dairy goat sperm. These findings shed light on the processes underlying alterations in the proteome and sperm freezability, aiding further research on sperm cryopreservation.

Visual analysis of lung neuroendocrine tumors based on CiteSpace knowledge graph.

Objective: The relevant literatures in the field of pulmonary neuroendocrine tumor were analyzed to understand the lineage, hot spots and development trends of research in this tumor. Method: The Web of Science core collection was searched for English-language literature about neuroendocrine tumors of the lung published between 2000 and 2022. CiteSpace software was imported for visualization analysis of countries, institutions, co-cited authors and co-cited journals and sorting of high-frequency keywords, as well as co-cited references and keyword co-occurrence, clustering and bursting display. Results: A total of 594 publications on neuroendocrine tumours of the lung were available, from 2000 to 2022, with an overall upward trend of annual publications in the literature. Authors or institutions from the United States, Italy, Japan and China were more active in this field, but there was little cooperation among the major countries. Co-cited references and keyword co-occurrence and cluster analysis showed that research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis and treatment was a current research hotspot. The keyword bursts suggested that therapeutic approaches might be a key focus of future research into the field for pulmonary neuroendocrine tumors. Conclusion: Over these 20 years, research related to neuroendocrine tumors of the lung has increased in fervour, with research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis, and treatment being the main focus of research. Therapeutic treatments may be the future research trend in this field.

Luminescent Metal-Organic Framework for the Selective Detection of Aldehydes.

The detection of toxic, hazardous chemical species is an important task because they pose serious risks to either the environment or human health. Luminescent metal-organic frameworks (LMOFs) as alternative sensors offer rapid and sensitive detection of chemical species. Interactions between chemical species and LMOFs result in changes in the photoluminescence (PL) profile of the LMOFs which can be readily detected using a simple fluorometer. Herein, we report the use of a robust, Zn-based LMOF, [Zn5(µ3-OH)2(adtb)2(H2O)5·5 DMA] (Zn-adtb, LMOF-341), for the selective detection of benzaldehyde. Upon exposure to benzaldehyde, Zn-adtb experiences significant luminescent quenching, as characterized through PL experiments. Photoluminescent titration experiments reveal that LMOF-341 has a detection limit of 64 ppm and a Ksv value of 179 M-1 for benzaldehyde. Furthermore, we study the guest-host interactions that occur between LMOF-341 and benzaldehyde through in situ Fourier transform infrared and computational modeling employing density functional theory. The results show that benzaldehyde interacts more strongly with LMOF-341 compared to formaldehyde and propionaldehyde. Our combined studies also reveal that the mechanism of luminescence quenching originates from an electron-transfer process.

Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Magnetically Induced Binary Ferrocene with Oxidized Iron.

Ferrocene is perhaps the most popular and well-studied organometallic molecule, but our understanding of its structure and electronic properties has not changed for more than 70 years. In particular, all previous attempts of chemically oxidizing pure ferrocene by binding directly to the iron center have been unsuccessful, and no significant change in structure or magnetism has been reported. Using a metal organic framework host material, we were able to fundamentally change the electronic and magnetic structure of ferrocene to take on a never-before observed physically stretched/bent high-spin Fe(II) state, which readily accepts O2 from air, chemically oxidizing the iron from Fe(II) to Fe(III). We also show that the binding of oxygen is reversible through temperature swing experiments. Our analysis is based on combining Mößbauer spectroscopy, extended X-ray absorption fine structure, in situ infrared, SQUID, thermal gravimetric analysis, and energy dispersive X-ray fluorescence spectroscopy measurements with ab initio modeling.

Rehabilitation effects of game therapy in people living with dementia: A systematic review and meta-analysis: Three formats of game therapy for Alzheimer's patients.

BACKGROUND: As a devastating neurodegenerative disease, Alzheimer's disease (AD) imposes a considerable direct and indirect financial burden. However, effective drug treatment options are limited. In recent years, game therapy has become a research hotspot in this field. AIMS: The purpose of this study was to synthesize the conclusions of existing studies and integrate the data to evaluate the effects of game therapy on people living with dementia (PLWD). METHODS: We included randomized clinical trials and quasi-experimental studies which assessed the impacts of game therapy on PLWD and took cognitive function, quality of life, and depression as outcome indicators. Two trained researchers independently screened the studies, evaluated the quality, and extracted the data. Statistical analysis was performed by Review Manager (Revman) 5.3 and STATA16.0 software. RESULTS: There were 12 studies involving 877 PLWD included, total. The results of the meta-analysis demonstrated that the Mini-Mental State Examination (MMSE) scores of the test group were significantly higher than that of the control group (SMD = 2.69, 95% CI [1.88, 3.51], p < .01), and the Cornell Scale for Depression in Dementia scores of the test group were significantly lower than those of the control group (SMD = -4.28, 95% CI [-6.96, -1.60], p < .01); but in terms of quality of life (SMD = 0.17, 95% CI [-0.82, 1.16], p = .74), the difference was not statistically significant. LINKING EVIDENCE TO ACTION: Game therapy can improve cognitive function and depression in PLWD. The combination of different types of games can improve the different clinical symptoms of PLWD, and different intervention time also have different effects on the outcome, which shows that we can develop unique, systematic, safe, and scientific game intervention programs for PLWD to improve their cognitive function and depression.

Anthropogenic land-use activities within watersheds reduce comammox activity and diversity in rivers.

Nitrogen cycling plays a key role in maintaining river ecological functions which are threatened by anthropogenic activities. The newly discovered complete ammonia oxidation, comammox, provides novel insights into the ecological effects of nitrogen on that it oxidizes ammonia directly to nitrate without releasing nitrite as canonical ammonia oxidization conducted by AOA or AOB which is believed to play an important role in greenhouse gas generation. Theoretically, contribution of commamox, AOA and AOB to ammonia oxidization in rivers might be impacted by anthropogenic land-use activities through alterations in flow regime and nutrient input. While how land use pattern affects comammox and other canonical ammonia oxidizers remains elusive. In this study, we examined the ecological effects of land use practices on the activity and contribution of three distinctive groups of ammonia oxidizers (AOA, AOB, comammox) as well as the composition of comammox bacterial communities from 15 subbasins covering an area of 6166 km2 in North China. The results showed that comammox dominated nitrification (55.71%-81.21%) in less disturbed basins characterized by extensive forests and grassland, while AOB became the major player (53.83%-76.43%) in highly developed basins with drastic urban and agricultural development. In addition, increasing anthropogenic land use activities within the watershed lowered the alpha diversity of comammox communities and simplified the comammox network. Additionally, the alterations of NH4+-N, pH and C/N induced by land use change were found to be crucial drivers in determining the distribution and activity of AOB and comammox. Together, our findings cast a new light on aquatic-terrestrial linkages from the view of microorganism-mediated nitrogen cycling and can further be applied to target watershed land use management.

Nitrite-resistance mechanisms on wastewater treatment in denitrifying phosphorus removal process revealed by machine learning, co-occurrence, and metagenomics analysis.

Nitrite is a key intermediate in nitrogen metabolism that determines microbial transformations of N and P, greenhouse gas (N2O) emissions, and system nutrient removal efficiency. However, nitrite also exerts toxic effects on microorganisms. A lack of understanding of high nitrite-resistance mechanisms at community- and genome-scale resolutions hinders the optimization for robustness of wastewater treatment systems. Here, we established nitrite-dependent denitrifying and phosphorus removal (DPR) systems under a gradient concentration of nitrite (0, 5, 10, 15, 20, and 25 mg N/L), relying on 16S rRNA gene amplicon and metagenomics to explore high nitrite-resistance mechanism. The results demonstrated that specific taxa were adopted to change the metabolic relationship of the community through phenotypic evolution to resist toxic nitrite contributing to the enhancement of denitrification and inhibition of nitrification and phosphorus removal. The key specific species, Thauera enhanced denitrification, whereas Candidatus Nitrotoga decreased in abundance to maintain partial nitrification. The extinction of Candidatus Nitrotoga induced a simpler restructuring-community, forcing high nitrite-stimulating microbiome to establish a more focused denitrification rather than nitrification or P metabolism in response to nitrite toxicity. Our work provides insights for understanding microbiome adaptation to toxic nitrite and giving theoretical support for operation strategy of nitrite-based wastewater treatment technology.

Anchoring Co3O4 nanoparticles on conjugated polyimide ultrathin nanosheets: construction of a Z-scheme nano-heterostructure for enhanced photocatalytic performance.

Efficient utilization of solar energy for photocatalytic hydrogen production and degradation of organic pollutants is one of the most promising approaches to solve the energy shortage and environmental pollution. A series of Co3O4/sulfur-doped polyimide (CO/SPI) direct Z-scheme nano-heterostructure photocatalysts was successfully prepared via a facile green thermal treatment method. The effects of Co3O4 nanoparticles on the structure, morphology, and optoelectronic properties of CO/SPI composite samples were systematically characterized by different spectroscopic methods. Characterization results confirmed that Co3O4 nanoparticles as an acid oxide catalyst promoted the oxidation stripping of bulk SPI to form SPI ultrathin nanosheets. Thus, the Co3O4 nanoparticles were firmly embedded on SPI ultrathin nanosheets to construct a direct Z-type CO/SPI nanostructure junction. Therefore, the activity and cycle stability of photocatalytic water splitting for hydrogen production and organic pollutant degradation were greatly improved under solar light irradiation. In particular, the 0.5CO/SPI composite sample displayed the highest activity with an average production rate of 127.2 µmol g-1 h-1, which is nearly 13 times and 106 times higher than that of SPI and Co3O4. This work provides a new avenue for constructing efficient inorganic-organic nanoheterostructured Z-type photocatalysts and takes an important step towards the efficient utilization of renewable energy.

Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment.

Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which has shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse effects limit the use of anti-PD1/PD-L1 antibodies. Here, we report the discovery and identification of S4-1, an innovative small-molecule inhibitor of PD-L1. In vitro, S4-1 effectively altered the PD-L1/PD-1 interaction, induced PD-L1 dimerization and internalization, improved its localization to endoplasmic reticulum, and thus enhanced the cytotoxicity of peripheral blood mononuclear cells toward tumor cells. In vivo, S4-1 significantly inhibited tumor growth in both lung and colorectal cancer models, particularly in colorectal cancer, where it led to complete clearance of a portion of the tumor cells. Furthermore, S4-1 induced T-cell activation and inversed the inhibitory tumor microenvironment, consistent with the PD-L1/PD-1 pathway blockade. These data support the continued evaluation of S4-1 as an alternative ICB therapeutic strategy.