Atopic Dermatitis and Psoriasis: Similarities and Differences in Metabolism and Microbiome.

Atopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain, scaly lesions, and histologically, acanthosis and hyperkeratosis. Meanwhile, they are both commonly comorbid with metabolic disorders such as obesity and diabetes, indicating that both diseases may exist with significant metabolic disturbances. Metabolomics reveals that both atopic dermatitis and psoriasis have abnormalities in a variety of metabolites, including lipids, amino acids, and glucose. Meanwhile, recent studies have highlighted the importance of the microbiome and its metabolites in the pathogenesis of atopic dermatitis and psoriasis. Metabolic alterations and microbiome dysbiosis can also affect the immune, inflammatory, and epidermal barrier, thereby influencing the development of atopic dermatitis and psoriasis. Focusing on the metabolic and microbiome levels, this review is devoted to elaborating the similarities and differences between atopic dermatitis and psoriasis, thus providing insights into the intricate relationship between both conditions.

3D Porous Fibers with Spatial Traps and Excellent Zn2+ Transport Kinetics Enable Stable Zn-Based Aqueous Battery.

Adverse side reactions and uncontrolled Zn dendrites growth are the dominant factors that have restricted the application of Zn ion batteries. Herein, a 3D self-supporting porous carbon fibers (denoted as PCFs) host is developed with "trap" effect to adjust the Zn deposition. The unique open structural design of N-doped carbon can act as the zincophilic sites to induce uniform deposition and inhibit adverse side reactions. More importantly, the porous hollow PCFs host with "trap" effect can induce Zn deposition in the fiber by adjusting the local electric field and current density, thereby increasing the specific energy density of the battery and inhibiting dendrite growth. In addition, the 3D open frameworks can regulate Zn2+ flux to enable outstanding cycling performance at ultra-high current densities. As expected, the PCFs framework guarantees the uniform Zn plating and stripping with an outstanding stability over 6000 cycles at the current density of 40 mA cm-2. And the Zn@PCFs||MnO2 full battery shows an excellent lifespan over 1300 cycles at 2000 mA g-1.

Socioeconomic disparity in the natural history of cutaneous melanoma: evidence from two large prospective cohorts.

BACKGROUND: Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design. METHODS: Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB. RESULTS: In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors. CONCLUSION: SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators.

Influence of climatic variables on maize grain yield and its components by adjusting the sowing date.

Yield and its components are greatly affected by climate change. Adjusting the sowing date is an effective way to alleviate adverse effects and adapt to climate change. Aiming to determine the optimal sowing date of summer maize and clarify the contribution of climatic variables to grain yield and its components, a consecutive 4-year field experiment was conducted from 2016 to 2019 with four sowing dates at 10-day intervals from 5 June to 5 July. Analysis of historical meteorological data showed that more solar radiation (SR) was distributed from early June to mid-August, and the maximum temperature (Tmax) > 32°C appeared from early July to late August, which advanced and lasted longer in 1991-2020 relative to 1981-1990. Additionally, the precipitation was mainly distributed from early June to late July. The climate change in the growing season of summer maize resulted in optimal sowing dates ranging from 5 June to 15 June, with higher yields and yield stability, mainly because of the higher kernel number per ear and 1,000-grain weight. The average contribution of kernel number per ear to grain yield was 58.7%, higher than that of 1,000-grain weight (41.3%). Variance partitioning analysis showed that SR in 15 days pre-silking to 15 days post-silking (SS) and silking to harvest (SH) stages significantly contributed to grain yield by 63.1% and 86.4%. The extreme growing degree days (EDD) > 32°C, SR, precipitation, and diurnal temperature range (DTR) contributed 20.6%, 22.9%, 14.5%, and 42.0% to kernel number per ear in the SS stage, respectively. Therefore, we concluded that the early sowing dates could gain high yield and yield stability due to the higher SR in the growing season. Meanwhile, due to the decreasing trend in SR and increasing Tmax trend in this region, in the future, new maize varieties with high-temperature resistance, high light efficiency, shade tolerance, and medium-season traits need to be bred to adapt to climate change and increased grain yield.

Arsenic distribution characteristics and release mechanisms in aquaculture lake sediments.

It is well known that aquaculture can alter the microenvironments of lakes at sediment-water interface (SWI). However, the main mechanisms underlying the effects of aquaculture activities on arsenic (As) transformations are still unclear. In this context, the present study aims to investigate the variations in the sediment As contents in Yangcheng Lake, as well as to assess its chemical transformations, release fluxes, and release mechanisms. The results showed substantial spatial differences in the dissolved As concentrations in the sediment pore water. The As release fluxes at the SWI ranged from 1.32 to 112.09 µg/L, with an average value of 33.68 µg/L. In addition, the highest As fluxes were observed in the aquaculture areas. The transformation of crystalline hydrous Fe oxide-bound As to adsorbed-As in the aquaculture lake sediments increased the ability of As release. The Partial least squares path modeling results demonstrated the great contributions of organic matter (OM) to the As transformations by influencing the sediment microbial communities and Fe/Mn minerals. The changes in the As fractionation and competing adsorption increased the dissolved As concentrations in the 0-10 mm surface sediment. Non-specifically and specifically adsorbed As were the major sources of dissolved As in the sediments. Specifically, microbial reduction of As[V] and dissolution of Fe oxides increased the dissolved As concentrations at the SWI (20 to -20 mm). The results of the current study highlight the positive enhancement effects of aquaculture on As release from sediments.

Integrative transcriptome-proteome approach reveals key hypoxia-related features involved in the neuroprotective effects of Yang Xue oral liquid on Alzheimer's and Parkinson's disease.

Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action.

Joint shape/texture representation learning for cardiovascular disease diagnosis from magnetic resonance imaging.

Aims: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Cardiac image and mesh are two primary modalities to present the shape and structure of the heart and have been demonstrated to be efficient in CVD prediction and diagnosis. However, previous research has been generally focussed on a single modality (image or mesh), and few of them have tried to jointly consider the image and mesh representations of heart. To obtain efficient and explainable biomarkers for CVD prediction and diagnosis, it is needed to jointly consider both representations. Methods and results: We design a novel multi-channel variational auto-encoder, mesh-image variational auto-encoder, to learn joint representation of paired mesh and image. After training, the shape-aware image representation (SAIR) can be learned directly from the raw images and applied for further CVD prediction and diagnosis. We demonstrate our method on data from UK Biobank study and two other datasets via extensive experiments. In acute myocardial infarction prediction, SAIR achieves 81.43% accuracy, significantly higher than traditional biomarkers like metadata and clinical indices (left ventricle and right ventricle clinical indices of cardiac function like chamber volume, mass, and ejection fraction). Conclusion: Our mesh-image variational auto-encoder provides a novel approach for 3D cardiac mesh reconstruction from images. The extraction of SAIR is fast and without need of segmentation masks, and its focussing can be visualized in the corresponding cardiac meshes. SAIR archives better performance than traditional biomarkers and can be applied as an efficient supplement to them, which is of significant potential in CVD analysis.

Design and Discovery of New Collagen V-Derived FGF2-Blocking Natural Peptides Inhibiting Lung Squamous Cell Carcinoma In Vitro and In Vivo.

Aberrant FGF2/FGFR signaling is implicated in lung squamous cell carcinoma (LSCC), posing treatment challenges due to the lack of targeted therapeutic options. Designing drugs that block FGF2 signaling presents a promising strategy different from traditional kinase inhibitors. We previously reported a ColVα1-derived fragment, HEPV (127AA), that inhibits FGF2-induced angiogenesis. However, its large size may limit therapeutic application. This study combines rational peptide design, molecular dynamics simulations, knowledge-based prediction, and GUV and FRET assays to identify smaller peptides with FGF2-blocking properties. We synthesized two novel peptides, HBS-P1 (45AA) and HBS-P2 (66AA), that retained the heparin-binding site. Both peptides demonstrated anti-LSCC and antiangiogenesis properties in cell viability and microvessel network induction assays. In two LSCC subcutaneous models, HBS-P1, with its affinity for FGF2 and enhanced penetration ability, demonstrated substantial therapeutic potential without apparent toxicities. Our study provides the first evidence supporting the development of collagen V-derived natural peptides as FGF2-blocking agents for LSCC treatment.

WHO global research priorities for sexually transmitted infections.

Sexually transmitted infections (STIs) are widespread worldwide and negatively affect sexual and reproductive health. Gaps in evidence and in available tools have long hindered STI programmes and policies, particularly in resource-limited settings. In 2022, WHO initiated a research prioritisation process to identify the most important STI research areas to address the global public health need. Using an adapted Child Health and Nutrition Research Initiative methodology including two global stakeholder surveys, the process identified 40 priority STI research needs. The top priorities centred on developing and implementing affordable, feasible, rapid point-of-care STI diagnostic tests and new treatments, especially for gonorrhoea, chlamydia, and syphilis; designing new multipurpose prevention technologies and vaccines for STIs; and collecting improved STI epidemiologic data on both infection and disease outcomes. The priorities also included innovative programmatic approaches, such as new STI communication and partner management strategies. An additional six research areas related to mpox (formerly known as monkeypox) reflect the need for STI-related research during disease outbreaks where sexual transmission can have a key role. These STI research priorities provide a call to action for focus, investment, and innovation to address existing roadblocks in STI prevention, control, and management to advance sexual and reproductive health and wellbeing for all.

Fructose-1,6-bisphosphatase deficiency: estimation of prevalence in the Chinese population and analysis of genotype-phenotype association.

Objective: Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inborn error due to mutations in the FBP1 gene. The genetic spectrum of FBP1D in China is unknown, also nonspecific manifestations confuse disease diagnosis. We systematically estimated the FBP1D prevalence in Chinese and explored genotype-phenotype association. Methods: We collected 101 FBP1 variants from our cohort and public resources, and manually curated pathogenicity of these variants. Ninety-seven pathogenic or likely pathogenic variants were used in our cohort to estimate Chinese FBP1D prevalence by three methods: 1) carrier frequency, 2) permutation and combination, 3) Bayesian framework. Allele frequencies (AFs) of these variants in our cohort, China Metabolic Analytics Project (ChinaMAP) and gnomAD were compared to reveal the different hotspots in Chinese and other populations. Clinical and genetic information of 122 FBP1D patients from our cohort and published literature were collected to analyze the genotype-phenotypes association. Phenotypes of 68 hereditary fructose intolerance (HFI) patients from our previous study were used to compare the phenotypic differences between these two fructose metabolism diseases. Results: The estimated Chinese FBP1D prevalence was 1/1,310,034. In the Chinese population, c.490G>A and c.355G>A had significantly higher AFs than in the non-Finland European population, and c.841G>A had significantly lower AF value than in the South Asian population (all p values < 0.05). The genotype-phenotype association analyses showed that patients carrying homozygous c.841G>A were more likely to present increased urinary glycerol, carrying two CNVs (especially homozygous exon1 deletion) were often with hepatic steatosis, carrying compound heterozygous variants were usually with lethargy, and carrying homozygous variants were usually with ketosis and hepatic steatosis (all p values < 0.05). By comparing to phenotypes of HFI patients, FBP1D patients were more likely to present hypoglycemia, metabolic acidosis, and seizures (all p-value < 0.05). Conclusion: The prevalence of FBP1D in the Chinese population is extremely low. Genetic sequencing could effectively help to diagnose FBP1D.

Multi-Shell Nanourchin-Integrated Dual Mode Lateral Flow Immunoassay for Sensitive and Rapid Detection of Clinical Cardiac Myosin-Binding Protein C.

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 109, which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Physical exercise-related manifestations of long COVID: A systematic review and meta-analysis.

Objective: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors. Methods: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis. Results: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO2max), and anaerobic threshold were impaired in COVID-19 survivors 3 months post-infection compared with non-COVID-19 controls in exercise testing, while VO2 were comparable between the two groups at rest. In contrast, no differences were observed in SpO2, heart rate, blood pressure, fatigue, and dyspnea between COVID-19 survivors and non-COVID-19 controls in exercise testing. Conclusion: The findings suggest an underestimation of the manifestations of PASC. COVID-19 survivors also harbor physical exercise-related symptoms of PASC that can be determined by the exercise testing and are distinct from those observed at rest. Exercise testing should be included while evaluating the symptoms of PASC in COVID-19 survivors.

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT.

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) in vitro and in vivo, as well as in atherosclerotic patients' arteries. Mechanistically, the histone chaperone ASF1A was first identified as a cofactor of P300, which precisely regulated the enrichment of H3K18la at the promoter of SNAI1, thereby activating SNAI1 transcription and promoting EndMT. We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction. Functional analysis based on Apoe KO Asf1a ECKO mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endothelium-specific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development. Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la, SNAI1 transcription, and EndMT-induced atherosclerosis. This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis, which provides emerging therapies for atherosclerosis.

Molecular and therapeutic landscape of ferroptosis in skin diseases.

ABSTRACT: Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis's role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Further screening of SNP loci of eggshell translucency related genes and evaluation of genetic effects.

Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency.

A Femtosecond Electron-Based Versatile Microscopy for Visualizing Carrier Dynamics in Semiconductors Across Spatiotemporal and Energetic Domains.

Carrier dynamics detection in different dimensions (space, time, and energy) with high resolutions plays a pivotal role in the development of modern semiconductor devices, especially in low-dimensional, high-speed, and ultrasensitive devices. Here, a femtosecond electron-based versatile microscopy is reported that combines scanning ultrafast electron microscopy (SUEM) imaging and time-resolved cathodoluminescence (TRCL) detection, which allows for visualizing and decoupling different dynamic processes of carriers involved in surface and bulk in semiconductors with unprecedented spatiotemporal and energetic resolutions. The achieved spatial resolution is better than 10 nm, and the temporal resolutions for SUEM imaging and TRCL detection are ≈500 fs and ≈4.5 ps, respectively, representing state-of-the-art performance. To demonstrate its unique capability, the surface and bulk carrier dynamics involved in n-type gallium arsenide (GaAs) are directly tracked and distinguished. It is revealed, in real time and space, that hot carrier cooling, defect trapping, and interband-/defect-assisted radiative recombination in the energy domain result in ordinal super-diffusion, localization, and sub-diffusion of carriers at the surface, elucidating the crucial role of surface states on carrier dynamics. The study not only gives a comprehensive physical picture of carrier dynamics in GaAs, but also provides a powerful platform for exploring complex carrier dynamics in semiconductors for promoting their device performance.

The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.

The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places aerobic glycolysis in a dominant position, the TCA cycle remains indispensable for tumor cells as a hub for the metabolic linkage and interconversion of glucose, lipids, and certain amino acids. TCA intermediates such as citrate, α-ketoglutarate, succinate, and fumarate are altered in tumors, and they regulate the tumor metabolism, signal transduction, and immune environment to affect tumorigenesis and tumor progression. This article provides a comprehensive review of the modifications occurring in tumor cells in relation to the intermediates of the TCA cycle, which affects tumor pathogenesis and current therapeutic strategy for therapy through targeting TCA cycle in cancer cells.