Long-Term Survival and Immune Reconstitution of Donor-Derived Chimeric Antigen Receptor T-Cell Therapy for Childhood Molecular Relapse of B-Cell Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp3)-H Bonds with CO2: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids.

Direct carboxylation of C-H bonds with CO2 represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp3)-H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp3)-H bonds with CO2 via visible-light photoredox catalysis. Various all-carbon quaternary carboxylic acids, which are of significant importance in medicinal chemistry, are successfully obtained with high yields. This direct carboxylation is characterized by good functional group tolerance, broad substrate scope, and mild operational conditions. Furthermore, our methodology enables the efficient and rapid synthesis of key drug or bioactive molecules, such as carbetapentane, caramiphen, and PRE-084 (σ1 receptor agonist), and facilitates various functionalizations of C(sp2)-H bonds using the directing ability of target carboxylic acids, thus highlighting its practical applications. Mechanistic studies indicate that a carbanion, which serves as the key intermediate to react with CO2, is catalytically generated via a single electron reduction of a benzylic radical through a consecutive photoinduced electron transfer process.

Inhalation of Microplastics Induces Inflammatory Injuries in Multiple Murine Organs via the Toll-like Receptor Pathway.

Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.

[Etiological analysis of hydronephrosis in adults: A single-center cross-sectional study].

OBJECTIVE: To investigate the etiological distribution of hydronephrosis caused by upper urinary tract obstruction in adult patients and to improve the diagnostic accuracy for this condition. METHODS: The clinical information of adult patients with newly diagnosed hydronephrosis in Upper Urinary Tract Repair Outpatient Clinic of Peking University First Hospital from May 2020 to May 2021 were prospectively and continuously collected. Patients with ureteral calculi or upper urinary tract tumor were excluded. A total of 767 patients were involved. The underlying causes of upper urinary tract obstruction were identified by senior urological surgeons according to symptoms, medical history, physical examination, and a range of diagnostic imaging techniques including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), retrograde pyelography, antegrade pyelography, radionuclide renogram and ureteroscopy. RESULTS: Among the 767 patients, 359(46.8%) were male and 408(53.2%) were female. The median age of these patients was 37 years (range, 14-84 years). Hydronephrosis was observed at left-sided in 357 cases(46.6%), right-sided in 251 cases(32.7%), and bilateral in 159 cases(20.7%). The causes of hydronephrosis were classified as follows: (1) Non-iatrogenic factors were found in 464 cases (60.5%). These included urinary malformations in 355 cases(76.5%), infection in 29 cases(6.3%), pelvic lipomatosis and/or cystitis glandularis in 23 cases(5.0%), ureteral endometriosis in 18 cases(3.9%), retroperitoneal fibrosis in 15 cases(3.2%), trauma in 7 cases(1.5%) and other non-iatrogenic factors in 12 cases(2.6%). Some of these patients had multiple non-iatrogenic causes. Among the 355 cases with urinary system malformations, 252 cases (71.0%) had ureteropelvic junction obstruction. (2) Iatrogenic ureteral injuries accounted for 210 cases (27.4%), including 112 cases(53.3%) of urological surgical injuries, 51 cases(24.3%) of radiotherapy for malignant tumor related injuries, 34 cases(16.2%) of gynecological and obstetrical surgical injuries, and 13 cases(6.2%) of general surgical injuries. (3) The cause of hydronephrosis remained unknown in 93 cases(12.1%). CONCLUSION: Hydronephrosis in adults due to upper urinary tract obstruction has a diverse range of causes, with urinary malformations and iatrogenic ureteral injuries being significant contributors. Urological surgeon involved in upper urinary tract reconstruction should be familiar with these potential causes to facilitate accurate diagnosis and effective treatment.

A Review on Bi2WO6-Based Materials for Photocatalytic CO2 Reduction.

Photocatalytic reduction of CO2 (PCR) technology offers the capacity to transmute solar energy into chemical energy through an eco-friendly and efficacious process, concurrently facilitating energy storage and carbon diminution, this innovation harbors significant potential for mitigating energy shortages and ameliorating environmental degradation. Bismuth tungstate (Bi2WO6) is distinguished by its robust visible light absorption and distinctive perovskite-type crystal architecture, rendering it highly efficiency in PCR. In recent years, numerous systematic strategies have been investigated for the synthesis and modification of Bi2WO6 to enhance its photocatalytic performance, aiming to achieve superior applications. This review provides a comprehensive review of the latest research progress on Bi2WO6 based materials in the field of photocatalysis. Firstly, outlining the fundamental principles, associated reaction mechanisms and reduction pathways of PCR. Then, the synthesis strategy of Bi2WO6-based materials is introduced for the regulation of its photocatalytic properties. Furthermore, accentuating the extant applications in CO2 reduction, including metal-Bi2WO6, semiconductor-Bi2WO6 and carbon-based Bi2WO6 composites etc. while concludes with an examination of the future landscape and challenges faced. This review hopes to serve as an effective reference for the continuous improvement and implementation of Bi2WO6-based photocatalysts in PCR.

CTRP9: An Anti-Atherosclerotic Factor in ApoE Knockout Mice through Oxidative Stress Inhibition.

BACKGROUND: C1q/tumor necrosis factor-related protein-9 (CTRP9) is critically involved in the pathophysiology of metabolic and cardiovascular disorders. This investigation aimed to clarify the mechanism underlying the role of CTRP9 in atherosclerosis in apolipoprotein E (ApoE) knockout (KO) mice. METHODS: ApoE KO mice were fed a Western diet and injected with a virus which resulted in CTRP9 overexpression or knockdown for 12 weeks. The plasma lipid levels and atherosclerotic plaque areas were measured after the mice were euthanized. Aortas were isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, plasma oxidative stress factors were measured to demonstrate the reliability of the RNA sequencing results. RESULTS: The plasma lipid levels in the CTRP9 overexpression group did not significantly differ from those in the green fluorescence protein (GFP) group. Markablely, CTRP9 overexpression inhibited atherosclerotic plaque formation in ApoE KO mice, whereas CTRP9 knockdown promoted plaque formation. RNA sequencing analysis identified 3485 differentially expressed genes that were prominently enriched across 55 signaling pathways. Additionally, plasma oxidative stress factors were significantly reduced after CTRP9 overexpression, whereas these factors were increased after CTRP9 knockdown, which was consistent with the results of the RNA sequencing analysis. CONCLUSIONS: These findings demonstrated that CTRP9 alleviated inflammation and cholesterol metabolism, which reduced oxidative stress in an atherosclerotic animal model. These beneficial effects may mediate the suppression of lesion development in the aorta.

Chrysomycin A Reshapes Metabolism and Increases Oxidative Stress to Hinder Glioblastoma Progression.

Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.

Pulmonary abscess caused by Streptococcus pseudopneumoniae in a child: A case report and review of literature.

BACKGROUND: Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children. Several pathogens can cause lung abscesses, with the most common pathogens being anaerobes, Streptococci and Staphylococcus aureus. Streptococcus pseudopneumoniae (S. pseudopneumoniae) is a member of the Streptococcaceae family, and is mainly isolated from respiratory tract specimens. There are currently no cases of lung abscess caused by S. pseudopneumoniae in the literature. CASE SUMMARY: A 2-year-old boy was admitted to hospital due to persistent cough and fever. Lung computed tomography examination suggested the formation of a lung abscess. His diagnosis was not confirmed by testing for serum respiratory pathogens (6 items), respiratory pathogen nucleic acid (27 items), and laboratory culture. Finally, metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S. pseudopneumoniae, confirming its role in causing the lung abscess. After receiving antibiotic treatment, reexamination with lung computed tomography showed that the abscess was resorbed and the patient's outcome was good. CONCLUSION: This is the first report of a lung abscess in a child caused by S. pseudopneumoniae infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.

Multicenter radio-multiomic analysis for predicting breast cancer outcome and unravelling imaging-biological connection.

Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Radiomics in breast cancer: Current advances and future directions.

Breast cancer is a common disease that causes great health concerns to women worldwide. During the diagnosis and treatment of breast cancer, medical imaging plays an essential role, but its interpretation relies on radiologists or clinical doctors. Radiomics can extract high-throughput quantitative imaging features from images of various modalities via traditional machine learning or deep learning methods following a series of standard processes. Hopefully, radiomic models may aid various processes in clinical practice. In this review, we summarize the current utilization of radiomics for predicting clinicopathological indices and clinical outcomes. We also focus on radio-multi-omics studies that bridge the gap between phenotypic and microscopic scale information. Acknowledging the deficiencies that currently hinder the clinical adoption of radiomic models, we discuss the underlying causes of this situation and propose future directions for advancing radiomics in breast cancer research.

Trifolium pratense as a novel phytogenic supplement, is an anticoccidial agent in chickens.

Coccidiosis, caused by a protozoan parasite of the genus Eimeria, is one of the most severe contagious parasite diseases affecting the poultry industry worldwide. Using phytogenics to prevent chicken coccidiosis is a strategy aimed at combating the increasing issue of drug-resistant strains of Eimeria spp. This study demonstrates the anticoccidial activities of a medicinal herb, Trifolium pratense (TP) powder, and its ethanolic extract (designated TPE) against Eimeria spp. TPE exhibited significant suppressive activity against E. maxima oocyst sporulation and E. tenella sporozoite invasion and reproduction in Madin-Darby bovine kidney cells. Furthermore, administration of basal chicken diets containing TP powder or TPE to Eimeria-infected chickens significantly reduced the output of oocysts and severity of intestinal lesions. Dietary supplementation with TP significantly improved relative weight gain in E. tenella- and E. acervulina-infected chickens, while there was no significant improvement in E. maxima-infected chickens. The anticoccidial activities of TP and TPE on E. acervulina, E. tenella and E. maxima were further supported by anticoccidial index scores, which showed greater efficacy than those of amprolium, a commercial coccidiostat used in poultry. TP supplementation positively impacted the primary metabolism of chickens challenged with E. tenella or E. acervulina. The chemical fingerprints of TPE were established using liquid column chromatography; TPE contained 4 major compounds: ononin, sissotrin, formononetin, and biochanin A. In addition, various spectrometric methods were used to ensure the batch-to-batch consistency of TP/TPE. In conclusion, T. pratense is demonstrated to be a novel phytogenic supplement that can be used to control Eimeria-induced coccidiosis in chickens.

Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer.

Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled-coil domain containing 6 [CCDC6]-rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N-thy-ori-3-1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low-dose IR-induced RET/PTC1 rearrangement in a dose-dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI-1, and Olaparib were employed to inhibit non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR-induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA-dependent protein kinase catalytic subunit (DNA-PKcs) decreased the efficiency of NHEJ and thus reduced IR-induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR-induced RET/PTC1 rearrangement. Targeting DNA-PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR-induced RET/PTC1 rearrangement in PTC.

Widely Targeted Metabolomic Analysis Reveals the Improvement in Panax notoginseng Triterpenoids Triggered by Arbuscular Mycorrhizal Fungi via UPLC-ESI-MS/MS.

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.

The anti-rheumatoid arthritic activity of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extract in collagen-induced arthritis in rats.

OBJECTIVES: Rheumatoid arthritis (RA) seriously affects the daily life of people. The whole plant of Artemisia ordosica Krasch. (AOK) has been used in folk medicine. This study aimed to investigate the in vivo anti-RA effects of AOK extract (AOKE) on collagen-induced arthritis in rats. METHODS: AOKE (400, 200, or 100 mg/kg) was administered orally to animals for 30 days. Body weight, paw swelling, arthritis index, thymus, and spleen indices, and pathological changes were assessed for effects of AOKE on RA. Furthermore, the inflammatory cytokines in rat serum were detected. In addition, the expressions of STAT3, Caspase-3, Galectin-3, and S100A9 in synovial tissue were researched using immunohistochemistry. KEY FINDINGS: The AOKE significantly reduced the arthritis indices, paw swelling, spleen, and thymus indices. Meanwhile, AOKE (400 mg/kg) decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-17A, and increased the level of IL-10 in rat serum. Histopathological examination showed that AOKE reduced inflammatory cell infiltration and cartilage erosion. Then, AOKE decreased the expressions of STAT3, Galectin-3, S100A9, and increased the expression of Caspase-3. CONCLUSION: AOKE had interesting anti-RA activity in rats, which deserved further research for the development and clinical use of this medicinal resource.

Decrotonylation of cGAS K254 prompts homologous recombination repair by blocking its DNA binding and releasing PARP1.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its interaction with PARP1, promoting homologous recombination repair. Moreover, SIRT3 suppression led to homologous recombination repair inhibition and markedly sensitized cancer cells to IR and DNA-damaging chemicals, highlighting SIRT3 as a potential target for cancer therapy. Overall, this study revealed the crucial role of cGAS crotonylation in the DNA damage response. Furthermore, we propose that modulating cGAS and SIRT3 activities could be potential strategies for cancer therapy.

Low-dose radiation promotes high-fat diet-induced atherosclerosis by activating cGAS signal pathway.

BACKGROUND: Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis. Whether the combination effect of HFD and LDR would have potential on atherosclerosis development remains incompletely unclear. METHODS: In this study, ApoE-/- mice were used as atherosclerosis model animals to investigate the combination effects of HFD and LDR (10 × 0.01Gy, or 20 × 0.01Gy) on vascular lesions. Doppler ultrasound imaging, H&E staining, oil red O staining, western blotting, and immunohistochemistry (IHC) were used to assess the pro-atherosclerotic effects. LC-MS was used to detect the non-targeted lipidomic. RESULTS: Long-term exposure of low-dose radiation at an accumulated dose of 0.2Gy significantly increased the occurrence of vascular stiffness and the aortic lesion in ApoE-/- mice. The synergistic effect of HFD and LDR was observed in the development of atherosclerosis, which might be linked to both the dysbiosis of lipid metabolism and the stimulation of the inflammatory signaling system. Moreover, LDR but not HFD can activate the cGAS-STING signaling through increasing the yield of cytosolic mitochondrial DNAs as well as the expression of cGAS protein. The activation of cGAS-STING signal triggers the release of IFN-α/-ß, which functions as an inflammatory amplifier in the formation of atherosclerotic plaque. CONCLUSION: The current study offers fresh insights into the risks and mechanism that underlie the development of atherosclerosis by LDR, and there is a combination effect of LDR and HFD with the involvement of cGAS-STING signal pathway.

Protein lysine crotonylation in cellular processions and disease associations.

Protein lysine crotonylation (Kcr) is one conserved form of posttranslational modifications of proteins, which plays an important role in a series of cellular physiological and pathological processes. Lysine ε-amino groups are the primary sites of such modification, resulting in four-carbon planar lysine crotonylation that is structurally and functionally distinct from the acetylation of these residues. High levels of Kcr modifications have been identified on both histone and non-histone proteins. The present review offers an update on the research progression regarding protein Kcr modifications in biomedical contexts and provides a discussion of the mechanisms whereby Kcr modification governs a range of biological processes. In addition, given the importance of protein Kcr modification in disease onset and progression, the potential viability of Kcr regulators as therapeutic targets is elucidated.