Expressed on the surface of CD8+ T cells, the CD8 co-receptor is a key component of the T cells that contributes to antigen recognition, immune cell maturation, and immune cell signaling. While CD8 is widely recognized as a co-stimulatory molecule for conventional CD8+ αβ T cells, recent reports highlight its multifaceted role in both adaptive and innate immune responses. In this review, we discuss the utility of CD8 in relation to its immunomodulatory properties. We outline the unique structure and function of different CD8 domains (ectodomain, hinge, transmembrane, cytoplasmic tail) in the context of the distinct properties of CD8αα homodimers and CD8αβ heterodimers. We discuss CD8 features commonly used to construct chimeric antigen receptors for immunotherapy. We describe the molecular interactions of CD8 with classical MHC-I, non-classical MHCs, and Lck partners involved in T cell signaling. Engineered and naturally occurring CD8 mutations that alter immune responses are discussed. The applications of anti-CD8 monoclonal antibodies (mABs) that target CD8 are summarized. Finally, we examine the unique structure and function of several CD8/mAB complexes. Collectively, these findings reveal the promising immunomodulatory properties of CD8 and CD8 binding partners, not only to uncover basic immune system function, but to advance efforts towards translational research for targeted immunotherapy.

Enterovirus 71 (EV71) is recognized as a major causative agent of hand, foot, and mouth disease (HFMD), posing a significant global public health concern due to its widespread impact and resulting in a major public health issue worldwide. Despite its prevalence, current clinical therapy lacks effective antiviral agents. Fucosylated chondroitin sulfates (FCS) derived from sea cucumber exhibits a range of biological activities including potent antiviral effects. This study provides compelling evidence of the potent antiviral efficacy of FCS against EV71. To further elucidate the impact of structural variations on the anti-EV71 activity, native FCSs with diverse sulfation patterns and a varity of FCS derivatives were prepared and analyzed. Notably, this study presents the detailed structural characterization of FCSs from the sea cucumbers Holothuria scabra Jaege and Holothuria fuscopunctata. Analysis of the structure-activity relationships revealed that molecular weight, sulfated fucose branches, and sulfation pattern were all crucial factors contributing to the potent inhibitory effects of FCS against EV71. Interestingly, molecular weight emerged as the most significant structural determinant of the antiviral potency. These findings suggest the promising potential of utilizing FCS as an innovative EV71 entry inhibitor for the treatment of HFMD.

The structure-function relationship of functionalized microcrystalline cellulose (MCC) composites as adsorbents remains unclear. Herein, the orange peel-derived MCC (i.e., OP-OH-H-25) was treated by different functional agents to prepare adsorbents for cadmium (Cd(II)) removal. Mercaptoacetic acid and orthophosphoric acid did not apparently impact MCC\'s surface site types and contents. Alternatively, they efficiently purified OP-OH-H-25 and generated OP-OH-SH and OP-OH-P samples with increased cellulose amounts. In contrast, the glycine modification produced OP-OH-NH2 with fewer sulfhydryl/carboxyl functional groups and more amide/amino sites. The pH-dependent Cd(II) removal trends by the MCC-related materials showed three successive stages with disparate sorption modes. The Cd(II) sorption kinetics processes on OP-OH-SH, OP-OH-P, and OP-OH-NH2 reached equilibrium after 0.25 h, faster than 0.5 h on OP-OH-H-25. The maximum Cd(II) sorption capacities of MCC-related adsorbents were OP-OH-P (151.81 mg/g) > OP-OH-SH (150.80 mg/g) > OP-OH-H-25 (124.90 mg/g) > > OP-OH-NH2 (55.23 mg/g). OP-OH-P exhibited the strongest Cd(II) sorption ability under the interference of mixed aquatic components. The intrinsic Cd(II) sorption mechanisms were identified as inner-sphere complexation and cation-π bond interaction. Overall, the select priority of modifying agents is orthophosphoric acid > mercaptoacetic acid > > glycine when preparing functionalized MCC adsorbents for purifying Cd(II)-polluted water systems.

The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF-κB signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.

Antimicrobial resistance poses a global health concern and develops a need to discover novel antimicrobial agents or targets to tackle this problem. Fluoroquinolone (FN), a DNA gyrase and topoisomerase IV inhibitor, has helped to conquer antimicrobial resistance as it provides flexibility to researchers to rationally modify its structure to increase potency and efficacy. This review provides insights into the rational modification of FNs, the causes of resistance to FNs, and the mechanism of action of FNs. Herein, we have explored the latest advancements in antimicrobial activities of FN analogues and the effect of various substitutions with a focus on utilizing the FN nucleus to search for novel potential antimicrobial candidates. Moreover, this review also provides a comparative analysis of two widely prescribed FNs that are ciprofloxacin and norfloxacin, explaining their rationale for their design, structure-activity relationships (SAR), causes of resistance, and mechanistic studies. These insights will prove advantageous for new researchers by aiding them in designing novel and effective FN-based compounds to combat antimicrobial resistance.

Fish sauce, derived from fermented fish, exhibits a notable antioxidant effect after a six-month fermentation process, and we propose that potential antioxidant peptides were present in the fish sauce. We isolated, purified, and identified potential bioactive antioxidant peptides by using fish sauce fermented for 6 months. Additionally, molecular simulation was employed to investigate the antioxidant action mechanism of these bioactive peptides. The molecular docking results revealed that FS4-1 (MHQLSKK), FS4-2 (VLDNSPER), FS4-3 (MNPPAASIK), FS6-1(VLKQAAAGR), and FS6-2 (SPDVSPRR), could dock with the Keap1 receptor. The primary force (Van der Waals\' force and hydrogen bonds) and key sites (GLY509 and ALA510) of Keap1 binding to peptides were determined. The active center was located in the side chain of amino acid Met at positions C7H78 and C7H79. We here identified antioxidant peptides in fish sauce and revealed the antioxidant mechanism through molecular simulations.

Overexpression of matrix metalloproteinase-2 (MMP-2) possesses a correlation with leukemia especially chronic myeloid leukemia (CML). However, no such MMP-2 inhibitor has come out in the market to date for treating leukemia. In this study, synthesis, biological evaluation, and molecular modeling studies of a set of biphenylsulfonamide derivatives as promising MMP-2 inhibitors were performed, focusing on their potential applications as antileukemic therapeutics. Compounds DH-18 and DH-19 exerted the most effective MMP-2 inhibition (IC50 of 139.45 nM and 115.16 nM, respectively) with potent antileukemic efficacy against the CML cell line K562 (IC50 of 0.338 µM and 0.398 µM, respectively). The lead molecules DH-18 and DH-19 reduced the MMP-2 expression by 21.3% and 17.8%, respectively with effective apoptotic induction (45.4% and 39.8%, respectively) in the K562 cell line. Moreover, both these compounds significantly arrested different phases of the cell cycle. Again, both these molecules depicted promising antiangiogenic efficacy in the ACHN cell line. Nevertheless, the molecular docking and molecular dynamics (MD) simulation studies revealed that DH-18 formed strong bidentate chelation with the catalytic Zn2+ ion through the hydroxamate zinc binding group (ZBG). Apart from that, the MD simulation study also disclosed stable binding interactions of DH-18 and MMP-2 along with crucial interactions with active site amino acid residues namely His120, Glu121, His124, His130, Pro140, and Tyr142. In a nutshell, this study highlighted the importance of biphenylsulfonamide-based novel and promising MMP-2 inhibitors to open up a new avenue for potential therapy against CML.

White rice consumption has been regarded as a potential risk factor for non-communicable diseases including obesity and type 2 diabetes. Thus, increasing attention has been paid to develop slowly digested rices with acceptable palatability. As the most abundant component of rice kernels, the fine molecular structure of starch controls not only the texture & aroma, but also the digestion properties of cooked rice. A large number of studies have been conducted to see what molecular structural features control the digestibility and palatability of cooked rice, which further could be connected to starch biosynthesis to enable rices with targeted functionalities to be chosen in non-empirical ways. Nonetheless, little progress has been made because of improper experimental designs. For example, the effects of starch fine molecular structure on cooked rice digestibility and palatability has been rarely studied within one study, resulting to various digestion results. Even for the same sample, it is hard to obtain consistent conclusions and sometimes, the results/coclusions are even controversy. In this review paper, starch fine molecular structural effects on the texture, aroma and starch digestion properties of cooked white rice were summarized followed by a detailed discussion of the relations between the fine molecular structures of amylopectin and amylose to deduce a more general conclusion of starch molecular structure-cooked rice property relations. It is expected that this review paper could provide useful information in terms of how to develop slowly digested rices with acceptable palatability.

Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, β-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, β-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, β-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010-present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.