Layer-Controllable "2.5D" DNA Origami Crystals Synthesized by a Hierarchical Assembly Strategy.

The finite periodic arrangement of functional nanomaterials on the two-dimensional scale enables the integration and enhancement of individual properties, making them an important research topic in the field of tuneable nanodevices. Although layer-controllable lattices such as graphene have been successfully synthesized, achieving similar control over colloidal nanoparticles remains a challenge. DNA origami technology has achieved remarkable breakthroughs in programmed nanoparticle assembly. Based on this technology, we proposed a hierarchical assembly strategy to construct a universal DNA origami platform with customized layer properties, which we called 2.5-dimensional (2.5D) DNA origami crystals. Methodologically, this strategy divides the assembly procedure into two steps: 1) array synthesis, and 2) lattice synthesis, which means that the layer properties, including layer number, interlayer distance, and surface morphology, can be flexibly customized based on the independent designs in each step. In practice, these synthesized 2.5D crystals not only pioneer the expansion of the DNA origami crystal library to a wider range of dimensions, but also highlight the technological potential for templating 2.5D colloidal nanomaterial lattices.

Bilateral Femtosecond Laser-Assisted Clear Lens Extraction with Trifocal Intraocular Lens Implantation for Presbyopia Correction: A Short-Term Observational Study in Chinese Adults.

Purpose: To observe the outcome of bilateral femtosecond laser-assisted clear lens extraction with trifocal intraocular lens (IOL) implantation for presbyopia correction and evaluate its feasibility in early presbyopic adults. Methods: Prospective case series of eyes with clear crystalline lenses that underwent femtosecond laser-assisted lens extraction and trifocal IOL (Acrysof IQ PanOptix, Model TFNT00, Alcon) implantation between 2021 and 2023 were followed up for at least 3 months after surgery. Outcome measures included monocular uncorrected visual acuity at near (UNVA, 40 cm), intermediate (UIVA, 60 cm), and distance (UDVA, 5 m), monocular manifest refraction, corrected distance visual acuity (CDVA), defocus curve assessment, and spectacle independence at both near and distance. Results: A total of 60 eyes from 30 consecutive patients were included, and their mean age was 50.4±6.5 years. After surgery, the mean UNVA (LogMAR) increased from 0.28±0.16 to 0.08±0.07, UIVA increased from 0.25±0.12 to 0.09±0.06, and UDVA increased from 0.27±0.21 to 0.01±0.08. The enhancements of UNVA, UIVA and UDVA were all significant (P < 0.05). The optometric results showed that the mean postoperative spherical equivalent (SE) was -0.21±0.24 D, and the mean postoperative CDVA (LogMAR) was -0.00±0.06. The preoperative spectacle independences at near and distance were 46.7% (14/30) and 56.7% (17/30), respectively, and both increased to 100% at 3 months after surgery. Conclusion: Satisfactory visual outcomes and safe surgical procedures were observed in this study, which demonstrate that bilateral femtosecond laser-assisted clear lens extraction with PanOptix IOL implantation could be a feasible approach for presbyopia correction in working-age Chinese patients.

Regulating Gelation and Luminescence Behaviors of Single Pyridine-Functionalized Cyanostilbene via Metal Ions.

Luminescent metal-organic gels (LMOGs) have gained much attention due to their crucial role in visual recognition and information encryption. However, it is still a challenge to simplify the design of ligands and enrich the stimuli responses in LMOGs simultaneously. Herein, although a single pyridine ligand cannot form gel alone, after coordination with metal ions, two kinds of LMOGs have been obtained with pyridine-metal complexes, where metal ions can act as cogelators and regulate luminescence of the pyridine-functionalized cyanostilbene ligand at the same time. The effects of metal types on the fluorescence emission color, the fluorescence quantum yield, the fibril network, and the assembly mode of the gel have been investigated systematically. In addition, two competitive ligands were used to regulate the fluorescence and phase transition of the gel. Finally, the logic gates and the information encryption and decryption have been successfully constructed. This kind of material is expected to be applied to fluorescence display, advanced information encryption, high-tech anticounterfeit, and so forth.

GY-SLAM: A Dense Semantic SLAM System for Plant Factory Transport Robots.

Simultaneous Localization and Mapping (SLAM), as one of the core technologies in intelligent robotics, has gained substantial attention in recent years. Addressing the limitations of SLAM systems in dynamic environments, this research proposes a system specifically designed for plant factory transportation environments, named GY-SLAM. GY-SLAM incorporates a lightweight target detection network, GY, based on YOLOv5, which utilizes GhostNet as the backbone network. This integration is further enhanced with CoordConv coordinate convolution, CARAFE up-sampling operators, and the SE attention mechanism, leading to simultaneous improvements in detection accuracy and model complexity reduction. While mAP@0.5 increased by 0.514% to 95.364, the model simultaneously reduced the number of parameters by 43.976%, computational cost by 46.488%, and model size by 41.752%. Additionally, the system constructs pure static octree maps and grid maps. Tests conducted on the TUM dataset and a proprietary dataset demonstrate that GY-SLAM significantly outperforms ORB-SLAM3 in dynamic scenarios in terms of system localization accuracy and robustness. It shows a remarkable 92.59% improvement in RMSE for Absolute Trajectory Error (ATE), along with a 93.11% improvement in RMSE for the translational drift of Relative Pose Error (RPE) and a 92.89% improvement in RMSE for the rotational drift of RPE. Compared to YOLOv5s, the GY model brings a 41.5944% improvement in detection speed and a 17.7975% increase in SLAM operation speed to the system, indicating strong competitiveness and real-time capabilities. These results validate the effectiveness of GY-SLAM in dynamic environments and provide substantial support for the automation of logistics tasks by robots in specific contexts.

Photoswitching in a Liquid Crystalline Pt(II) Coordination Complex.

Photoswitching of photoluminescence has sparked tremendous research interests for super-resolution imaging, high-security-level anti-counterfeiting, and other high-tech applications. However, the excitation of photoluminescence is usually ready to trigger the photoswitching process, making the photoluminescence readout unreliable. Herein, we report a new photoswitch by the marriage of spiropyran with platinum(II) coordination complex. Viable photoluminescence can be achieved upon excitation by 480 nm visible light while the photoswitching can be easily triggered by 365 nm UV light. The feasible photoswitching may be benefited from the formed liquid crystalline (LC) phase of the designed photoswitch as a crystalline spiropyran is normally unable to implement photoswitching. Compared to the counterparts, this LC photoswitch can show distinct and reliable apparent colors and emission colors before and after photoswitching, which may promise the utility in high-security-level anti-counterfeiting and other advanced information technologies.

Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection.

Although no longer a public health emergency of international concern, COVID-19 remains a persistent and critical health concern. The development of effective antiviral drugs could serve as the ultimate piece of the puzzle to curbing this global crisis. 3-chymotrypsin-like protease (3CLpro), with its substrate specificity mirroring that of the main picornavirus 3C protease and conserved across various coronaviruses, emerges as an ideal candidate for broad-spectrum antiviral drug development. Moreover, it holds the potential as a reliable contingency option to combat emerging SARS-CoV-2 variants. In this light, the approved drugs, promising candidates, and de-novo small molecule therapeutics targeting 3CLpro since the COVID-19 outbreak in 2020 are discussed. Emphasizing the significance of diverse structural characteristics in inhibitors, be they peptidomimetic or nonpeptidic, with a shared mission to minimize the risk of cross-resistance. Moreover, the authors propose an innovative optimization strategy for 3CLpro reversible covalent PROTACs, optimizing pharmacodynamics and pharmacokinetics to better prepare for potential future viral outbreaks.

Light-Responsive Supramolecular Liquid-Crystalline Metallacycle for Orthogonal Multimode Photopatterning.

The development of multimode photopatterning systems based on supramolecular coordination complexes (SCCs) is considerably attractive in supramolecular chemistry and materials science, because SCCs can serve as promising platforms for the incorporation of multiple functional building blocks. Herein, we report a light-responsive liquid-crystalline metallacycle that is constructed by coordination-driven self-assembly. By exploiting its fascinating liquid crystal features, bright emission properties, and facile photocyclization capability, a unique system with spatially-controlled fluorescence-resonance energy transfer (FRET) is built through the introduction of a photochromic spiropyran derivative, which led to the realization of the first example of a liquid-crystalline metallacycle for orthogonal photopatterning in three-modes, namely holography, fluorescence, and photochromism.

hsdSA regulated extracellular vesicle-associated PLY to protect Streptococcus pneumoniae from macrophage killing via LAPosomes.

IMPORTANCE: S. pneumoniae is a major human pathogen that undergoes a spontaneous and reversible phase variation that allows it to survive in different host environments. Interestingly, we found hsdSA , a gene that manipulated the phase variation, promoted the survival and replication of S. pneumoniae in macrophages by regulating EV production and EV-associated PLY. More importantly, here we provided the first evidence that higher EV-associated PLY (produced by D39) could form LAPosomes that were single membrane compartments containing S. pneumoniae, which are induced by integrin ß1/NOX2/ROS pathway. At the same time, EV-associated PLY increased the permeability of lysosome membrane and induced an insufficient acidification to escape the host killing, and ultimately prolonged the survival of S. pneumoniae in macrophages. In contrast, lower EV-associated PLY (produced by D39ΔhsdSA ) activated ULK1 recruitment to form double-layered autophagosomes to eliminate bacteria.

Postoperative Outcome of Combined Phacovitrectomy in Eyes with Excessive Myopia (>-30 D).

Background: To report the outcomes of phacoemulsification combined with vitrectomy in eyes with extreme myopia (-30 diopters or more). Case Presentation. Three patients with cataract, vitreous opacities, and extreme myopia of more than -30 diopters underwent a combined surgical procedure of cataract extraction combined with vitrectomy. Postoperative refractive correction of the three cases ranged from -1.0 D to -2.5 D spherical equivalent. There was an obvious hyperopic shift of all cases. All patients noted a significant improvement in uncorrected and best-corrected visual acuity from 0.4 to 0.8 in case 1, from CF/70 cm to 1.0 in case 2, and from 0.12 to 0.5 in the right eye and 0.15 to 0.2 in the left eye in case 3. Vitreous floaters disappeared in all cases. No complications were noted during follow-up. Conclusions: To the best of the authors' knowledge, these represent the first reported clinical cases of combined cataract extraction+vitrectomy surgery in eyes with extreme (>-30 D) myopia. Our results support the notion that phacoemulsification combined with vitrectomy may be a good therapeutic option for cataracts and vitreous floaters in cases with extreme myopia.

Naphthyl Substituted Impurities Induce Efficient Room Temperature Phosphorescence.

Accidentally, it was found that triphenylamine (TPA) from commercial sources shows ultralong yellow-green room temperature phosphorescence (RTP) like commercial carbazole, which however disappears for lab-synthesized TPA with high purity. Herein, we for the first time identify the impurity types that cause RTP of commercial TPA, which are two N, N-diphenyl-naphthylamine isomers. Due to similar molecular polarity and very trace amount (≈0.8 ‰, molar ratio), these naphthyl substituted impurities can be easily overlooked. We further show that even at an extremely low amount (1000000 : 1, mass ratio) of impurities, RTP emission is still generated, attributed to the triplet-to-triplet energy transfer mechanism. Notably, this doping strategy is also applicable to the triphenylphosphine and benzophenone host systems, of which strong RTP emission can be activated by simply doping the corresponding naphthyl substituted analogues into them. This work therefore provides a general and efficient host/guest strategy toward high performance and diverse organic RTP materials.

Anion receptor and heavy metal-free redox mediator decorated separator for lithium-sulfur batteries.

The adsorption-catalysis synergy for accelerated conversion of polysulfides is critical toward the electrochemical stability of lithium-sulfur battery (LSB). Herein, a non-metallic polymer network with anion receptor units, trifluoromethanesulfonyl (CF3SO2-) substituted aza-ether, was in-situ integrated on PE separator, working as an efficient host for anchoring lithium thiophosphates (LPS) as redox mediators and polysulfides through Lewis acid-base interaction. The anchored LPS on the modified PE separator displayed a robust chemical adsorption ability towards polysulfides through the formation of SS bond. Meanwhile, LPS decreased the energy barrier of Li2S nucleation and promoted redox reaction kinetics. The battery with LPS decorated separator revealed a long cycling lifespan with a per cycle decay of 0.056 % after 600 cycles, and a competitive initial capacity of 889.1 mAh/g when the of sulfur cathode increased to 3 mg cm-2. This work developed a new design strategy to promote the utilization of lithium phosphorus sulfide compounds in LSB.

Design, synthesis, and evaluation of novel pleuromutilin aryl acrylate derivatives as promising broad-spectrum antibiotics especially for combatting multi-drug resistant gram-negative bacteria.

The emergence of drug-resistant strains presents a grave challenge for traditional antibiotics, underscoring the exigency of exploring novel antibacterial drugs. To address this, the present study endeavors to design and synthesize a collection of pleuromutilin aromatic acrylate derivatives, guided by combination principles. The antibacterial activity and structure-activity relationship of these derivatives were evaluated, and most of the derivatives displayed moderate to excellent antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Among these derivatives, 5g exhibited the strongest antibacterial activity, with MIC (minimum inhibitory concentration) values ranging from 1-32 µg/mL, and a MIC value against clinically isolated drug-resistant strains of 4-64 µg/mL. Additionally, 5g exhibited negligible cytotoxicity, superior anti-mycoplasma activity, and a greater propensity to perturb bacterial cell membranes. Notably, the administration of 5g resulted in an increased survival rate of MRSA (Methicillin-resistant Staphylococcus aureus)-infected mice, with an ED50 (median effective dose) value of 9.04 mg/kg. These results indicated the potential of 5g to be further developed as an antibacterial drug for the clinical treatment of drug-resistant bacterial infections.

Phenylalanine-mediated changes in the soil bacterial community promote nitrogen cycling and plant growth.

Soil amino acids (AAs) are the most active components of soil N, which can be mineralized or absorbed by bacteria as N and C sources. We hypothesized that exogenous AAs could regulate the bacterial community and affect soil N cycling, and the effect sizes could vary depending on individual AAs. Here, we applied feather (keratin)-based compost rich in AAs to Poncirus trifoliata (L.) to evaluate the regulation of bacterial community by AAs; furthermore, we applied six individual AAs to test their effects. The compost significantly increased soil hydrolysable AA content, ammonia monooxygenase gene abundance, and plant growth and changed bacterial community structure. Redundancy analysis revealed that the effects of AAs on the bacterial community composition were greater than those of soil chemical properties, and phenylalanine (Phe) was the most effective among thirteen individual AAs. When applied individually, Phe caused the greatest increase in N cycling-related enzyme activity and plant growth and most significantly altered the bacterial community structure among the six exogenous AAs. Notably, Phe significantly increased the relative abundances of Burkholderia-Caballeronia-Paraburkholderia, Azospirillum, Cupriavidus, and Achromobacter, whose abundances were significantly positively correlated with plant biomass, and significantly reduced the relative abundances of Arachidicoccus, Pseudopedobacter, Sphingobacterium, and Paenibacillus, whose abundances were significantly negatively correlated with plant biomass. We demonstrate that soil AAs strongly shape the bacterial community. Particularly, Phe enhances N cycling and plant growth by increasing the potentially beneficial bacterial taxa and inhibiting the potentially harmful bacterial taxa, which needs further validation.

Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN. METHODS: Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected. RESULTS: CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs. CONCLUSIONS: CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.

Extending Conjugation of Linear Cyanostilbene Derivatives via a Pyridine Moiety for Multi-Stimuli-Responsive Fluorescence Organogels.

In the design of effective gelators with aggregation-induced emission behavior, amide and cholesterol moieties are generally used to provide multiple driving forces for gelation. In this work, a series of linear cyanostilbene gelators with a pyridine moiety and different lengths of the alkoxyl group, i.e., CSpy-Cn, have been synthesized through nucleophilic substitution and Knoevenagel reaction. The direct connection of pyridine extends the conjugation of the cyanostilbene moiety, while the alkoxyl group can regulate the solubility of the compounds so that the compounds can serve as gelators for common solvents such as acetonitrile, dimethyl sulfoxide, and ethanol at ultra-low concentrations. At the same time, the cyanostilbene group makes the compounds undergo photoisomerization and emit fluorescence under UV light, while the pyridine group can serve as an acid-base responsive group due to easy protonation. The gels can respond to temperature, light, and organic acid/base. The fluorescence intensity and color can reversibly change during the gel-sol transitions. Finally, a thin film based on the CSpy-C8 xerogel has been prepared and utilized as a multi-stimuli-responsive fluorescence display for information storage and anti-counterfeiting.

Supramolecular Liquid Crystal Carbon Dots for Solvent-Free Direct Ink Writing.

Recent years have witnessed the major advances of nanolights with extensive exploration of nano-luminescent materials like carbon dots (CDs). However, solvent-free processing of these materials remains a formidable challenge, impeding endeavors to develop advanced manufacturing techniques. Herein, in response to this challenge, liquid crystallization is demonstrated as a versatile and robust approach by deliberately anchoring flexible alkyl chains on the CDs surface. Alkyl chain grafting on the CDs surface is observed to substantially depress the common aggregation-caused quenching effect, and results in a shift of self-assembly structure from the crystalline phase to smectic liquid crystalline phase. The liquid-crystalline phase-transition temperature is ready to adjust by varying the alkyl chain length, endowing low-temperature (<50 °C) melt-processing capabilities. Consequently, the first case of direct ink writing (DIW) with liquid crystal (LC) carbon dots is demonstrated, giving rise to highly emissive objects with blue, green and red fluorescence, respectively. Another unexpected finding is that DIW with the LC inks dramatically outperforms DIW with isotropic inks, further highlighting the significance of the LC processing. The approach reported herein not only exhibits a fundamental advance by imparting LC functions to CDs, but also promises technological utility in DIW-based advanced manufacturing.

Cbf-14, a cationic peptide derived from cathelin-domain, exhibits anti-inflammation activity via inhibiting PI3K- Akt /ROS/ NF-κB signaling pathway.

Cbf-14 with the sequence RLLRKFFRKLKKSV, is an effective antimicrobial peptide derived from a cathelin-like domain. Previous reports have demonstrated that Cbf-14 not only exerts antimicrobial activity against penicillin-resistant bacteria but also alleviates bacterial-induced inflammation in E. coli BL21 (DE3)-NDM-1-infected mice. In this article, we demonstrated that Cbf-14 can effectively reduce RAW 264.7 intracellular infection caused by clinical strain E. coli and alleviate the inflammatory response of cells and improve cell survival after infection. Therefore, we established the LPS-stimulated RAW 264.7 cell inflammation model to uncover the molecular mechanisms of the peptide Cbf-14 in anti-inflammatory activity. The results reveal that Cbf-14 can decrease LPS-induced ROS secretion by blocking the membrane translocation of p47-phox subunits and suppressing p47-phox protein phosphorylation. Meanwhile, this peptide can down-regulate the over-expression of iNOS, and finally inhibit the NO excessive secretion from RAW 264.7 macrophages stimulated by LPS. Moreover, Cbf-14 also down-regulates the expression levels of p-IκB and p-p65 and inhibits the nuclear translocation of NF-κB through blocking MAPK- and/or PI3K-Akt signaling pathways. Overall, Cbf-14 exhibits anti-inflammatory activity through inhibiting NF-κB activity and ROS production via PI3K- Akt signaling pathway.

Effects of exogenous retinoic acid on ocular parameters in Guinea pigs with form deprivation myopia.

Aim: Myopia is a common chronic eye disease, this study is to investigate the effects of exogenous retinoic acid (RA) on intraocular parameters, especially choroidal thickness (CT) and retinal thickness (RT), in guinea pigs with form deprivation myopia (FDM). Methods: A total of 80 male guinea pigs were divided randomly into 4 groups: Control, FDM, FDM + RA, and FDM + Citral groups. The FDM + RA group was given 24 mg/kg RA dissolved in 0.4 mL peanut oil; the FDM + Citral group was given citral 445 mg/kg dissolved in 0.4 mL peanut oil; The other two groups were given 0.4 mL peanut oil. After 4 weeks, the refractive error (RE), axial length (AL), and intraocular pressure (IOP) of all guinea pigs were measured, and the parameters of RT and CT were obtained using enhanced depth imaging optical coherence tomography (EDI-OCT). Results: After 4 weeks, both the RE and AL in the FDM and FDM + RA groups were increased, and the RT and CT in both groups were smaller than those in the Control group (p < 0.05). Only the IOP of the right eye in the FDM + RA group increased significantly (p < 0.05). The RT of the right eye of the 4 groups was compared: Control group > FDM + Citral group > FDM group > FDM + RA group. Compared with the RT of the left eye and the right eye among the 4 groups, the RT of the right eye in the FDM and FDM + RA groups was significantly less than that in the left eye (p < 0.05). Moreover, the CT of the right eye in the Control group was greater than that in the other three groups (p < 0.0001). There was no significant difference in the CT among the FDM, FDM + RA, and FDM + Citral groups (p > 0.05). In contrast to the RT results, the CT results of the left and right eyes in the FDM + Citral group showed statistically significant differences (p < 0.05). Conclusion: RA participates in the progression of FDM as a regulatory factor. Exogenous RA can increase the RE, AL, and IOP of FDM guinea pigs, and might aggravate the retinal thinning of FDM guinea pigs. Citral can inhibit these changes, but RA might not affect the thickness of the choroid.

A Review on Low-Molecular-Weight Gels Driven by Halogen-Effect.

As a new type of non-covalent interaction similar to hydrogen bond, halogen bond has become an important supramolecular tool in crystal engineering, material chemistry, biological science, etc., due to its unique properties. In fact, halogen bond has been confirmed on the effect of molecular assemblies and soft materials, and widely used in various functional soft materials including liquid crystals, gels and polymers. In recent years, halogen bonding has aroused strong interest in inducing molecular assembly into low-molecular-weight gels (LMWGs). To the best of our knowledge, there is still a lack of in-depth review of this field. So, in this paper, the recent progress of LMWGs driven by halogen bonding is reviewed. According to the number of components forming halogen bonded gels, the structural characteristics of halogen bonded supramolecular gels, the relationship between halogen bonding and other non-covalent interactions, as well as the application fields of halogen bonded gels are introduced, respectively. In addition, the challenges faced by halogenated supramolecular gels at present and their development prospects in future have been proposed. We believe that the halogen bonded gel will have more impressive applications in the next few years, opening exciting new opportunities for the development of soft materials.

Increased co-expression of TIM-3 with TIGIT or 2B4 on CD8+ T cells is associated with poor prognosis in locally advanced nasopharyngeal carcinoma.

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma.