Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB.

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.

Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation.

BACKGROUND: Liver transplantation is treatment option for patients with end stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). METHODS: We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately prior to LDLT, and renal function status was followed up for 3 consecutive days postoperatively. RESULTS: Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early post-transplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. CONCLUSION: AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AK.

Effects of system parameters on a single-beam synthetic gradiometer with a dual-cell structure.

We report a single-beam synthetic gradiometer operated in the spin-exchange-relaxation free (SERF) regime, using the structure of two separate atomic vapor cells spaced 2 cm apart. To improve the capability of the gradiometer in suppressing the common-mode magnetic field noise, we are aiming at investigating the effects of the system parameters on the gradiometer common-mode rejection ratio (CMRR). The mathematical expression for the relationship between the gradiometer CMRR and the two variables including the linewidth ratio and the pumping factor ratio is constructed for the first time, to our knowledge. This means that the CMRR can be optimized by controlling the linewidth and the pumping factor, which is easy to implement in the operation process. As a result, a CMRR of 246 is achieved and a gradiometer sensitivity of 4.5 fT/cm/Hz1/2 is also measured. This method provides a theoretical and experimental basis for the automated operation of gradiometers, and the gradiometer system performance can be tuned to a desired state by simply controlling the linewidth and the incident light intensity.

Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC.

Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion.

INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration.

BACKGROUND: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown. METHODS AND RESULTS: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients. CONCLUSIONS: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.

Sensing patches for biomarker identification in skin-derived biofluids.

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).

Synthesis and properties of an O-doped aromatic belt.

A new macrocyclic arene, dibenzofuran[3]arene, was synthesized, which could be conveniently transformed to an O-doped aromatic belt with a rigid ring-shaped structure and deep cavity. Moreover, the O-doped aromatic belt also showed a high HOMO energy and a narrow HOMO-LUMO gap experimentally and theoretically.

Isobutyramide and Slow-Release Urea as Substitutes for Soybean Meal in the Finishing Diet of Beef Cattle.

Two experiments were conducted to investigate the effects of isobutyramide (IBA) and slow-release urea (SRU) as substitutes for soybean meal (SBM) in the finishing diet of beef cattle. The completely randomized design in vitro experiment with five treatments, i.e., control, 0.9% SRU group, 0.6% SRU + 0.3% IBA group (SRU-I), 0.3% SRU + 0.6% IBA group (IBA-S), 0.9% IBA group was conducted. The results showed that the IBA-S and IBA increased (p ≤ 0.05) substrate disappearance of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), total gas, and total volatile fatty acids (TVFA). The SRU group had the highest (p < 0.01) crude protein disappearance and ammonia nitrogen concentration, but the IBA contrarily decreased (p < 0.01) them compared with the control. Inclusion of IBA increased isobutyrate concentrations (p = 0.01) with the highest value for the IBA group. Then, an 84-day replicate 4 × 4 Latin square design with 8 Angus steers and four treatments, i.e., control, SRU, SRU-I, IBA-S was performed. The results showed that the treatments did not affect DM intake (p > 0.05) but tended (p = 0.09) to increase average daily gain. The inclusion of IBA increased (p < 0.05) the apparent digestibility of DM, organic matter, NDF, ADF, TVFA, and microbial crude protein with the highest values for the IBA-S group. The IBA-contained groups also increased (p ≤ 0.01) isobutyrate concentration, activities of carboxymethyl cellulase and xylanase, and the relative abundance of Butyrivibrio fibrisolvens with the highest values for the IBA-S group. The SRU had no effect on animal growth and nutrient apparent digestibility. In conclusion, IBA was developed as a new substitute for SBM in the finishing diet of beef cattle, and the optimal strategy was the isonitrogenous substitution of SBM with 0.3% SRU and 0.6% IBA of the diet.

LDL Receptor-Related Protein 1B Polymorphisms Associated with Increased Risk of Lymph Node Metastasis in Oral Cancer Group with Diabetes Mellitus.

Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC; p = 0.046) were significantly associated with tumor size compared with those with homozygous major alleles (AA). Similarly, compared to genotypes homologous for the main allele (GG), rs6742944 genotypes (GA + AA; p = 0.010) were more likely to develop lymph node metastases. The tongue and the rs6742944 genotypes (GA + AA) exhibited higher rates of advanced clinical stages (p = 0.024) and lymph node metastases (p = 0.007) when compared to homozygous alleles (GG). LRP1B genetic polymorphisms appear to be prognostic and diagnostic markers for OSCC and DM, as well as contributing to genetic profiling research for personalized medicine.

Racial Disparities in Selected Complications and Comorbidities among People with Type 2 Diabetes.

Type 2 diabetes (T2D) is a growing public health concern, disproportionately impacting racial and ethnic minorities. Assessing disparities is the first step towards achieving the translation goal to reduce disparities in diabetes outcomes, according to the Centers for Disease Control and Prevention (CDC)'s Division of Diabetes. We analyzed the data of patients (18+ years) diagnosed with T2D between 1 January 2012 and 31 March 2017, using the electronic health records of the University of Texas Medical Branch at Galveston. We compared the crude rate and age-standardized rate (using direct method) of selected micro- and macrovascular complication rates, associated obesity, and insulin dependence among racial and ethnic groups. Our sample included 20,680 patients who made 394,106 visits (9922 non-Hispanic White patients, 4698 non-Hispanic Black patients, and 6060 Hispanic patients). Our results suggest a higher risk of acquiring macrovascular (hypertension, ischemic disease, and stroke) and microvascular (renal, ophthalmic, and neurological) complications in Black patients compared to non-Hispanic White and Hispanic patients. The rates of stage I or II obesity were higher in Black patients compared with White and Hispanic patients. The rates of insulin use rather than oral hypoglycemics were also higher in Black patients than White and Hispanic patients. The disparities in terms of the higher susceptibility to complications among Black patients are possibly linked to the socioeconomic disadvantages of this population, leading to poorer management. Prevention strategies are warranted to reduce the incidence of T2D complications in racial minorities.

Research strategies of small molecules as chemotherapeutics to overcome multiple myeloma resistance.

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM.

Evaluation of a Standard Dietary Regimen Combined with Heat-Inactivated Lactobacillus gasseri HM1, Lactoferrin-Producing HM1, and Their Sonication-Inactivated Variants in the Management of Metabolic Disorders in an Obesity Mouse Model.

This study investigated the impact of incorporating various inactivated probiotic formulations, with or without recombinant lactoferrin (LF) expression, into a standard chow diet on metabolic-related disorders in obese mice. After inducing obesity through a 13-week high-fat diet followed by a standard chow diet, mice received daily oral administrations of different probiotics for 6 weeks using the oral gavage approach. These probiotic formulations consisted of a placebo (MRS), heat-inactivated Lactobacillus gasseri HM1 (HK-HM1), heat-killed LF-expression HM1 (HK-HM1/LF), sonication-killed HM1 (SK-HM1), and sonication-killed LF-expression HM1 (SK-HM1/LF). The study successfully induced obesity, resulting in worsened glucose tolerance and insulin sensitivity. Interestingly, the regular diet alone improved glucose tolerance, and the addition of inactivated probiotics further enhanced this effect, with SK-HM1/LF demonstrating the most noticeable improvement. However, while regular dietary intervention alone improved insulin sensitivity, probiotic supplementation did not provide additional benefits in this aspect. Inflammation in perirenal and epididymal fat tissues was partially alleviated by the regular diet and further improved by probiotics, particularly by SK-HM1, which showed the most significant reduction. Additionally, HK-HM1 and HK-HM1/LF supplements could contribute to the improvement of serum total triglycerides or total cholesterol, respectively. Overall, incorporating inactivated probiotics into a regular diet may enhance metabolic indices, and recombinant LF may offer potential benefits for improving glucose tolerance.

The Protective Role of Vitamin E against Oxidative Stress and Immunosuppression Induced by Non-Esterified Fatty Acids in Bovine Peripheral Blood Leukocytes.

High levels of non-esterified fatty acids (NEFAs) during the transition period lead to increased oxidative stress and immunosuppression in cows. Feeding them a vitamin-E-supplemented diet reduces reactive oxygen species (ROS) levels in the blood and diminishes immunosuppression in the transition period. However, whether the restoration of immune cell function occurs through the direct action of vitamin E in cells is still a topic that requires further discussion. Therefore, in this experiment, we aimed to investigate the effect of NEFAs on peripheral blood leukocytes (PBLs) and whether vitamin E mitigates the impact of NEFAs. We employed three groups: (1) blank, (2) NEFA only, and (3) pre-culturing with vitamin E before NEFA treatment (VENEFA). In peripheral blood mononuclear cells (PBMCs), there were no differences in vitamin E content among the three groups. However, in the vitamin E pre-treatment group, the vitamin E levels of polymorphonuclear neutrophils (PMNs) were significantly higher than those in the other two groups. NEFA levels increased malondialdehyde (MDA) levels in PBMCs, but pre-treatment with vitamin E reduced accumulation of MDA levels. Regarding the expression of proinflammatory genes, NEFAs increased the expression of interleukin-1ß in PBMCs and colony-stimulating factor 2 in PMNs. Vitamin E pre-treatment restored the increase in interleukin-1ß levels caused by NEFAs in PBMCs. None of the groups affected the phagocytosis of PMNs. Few studies have confirmed that NEFAs cause oxidative stress in bovine PBLs. In summary, this study found that NEFAs induce oxidative stress in PBLs and alter the expression of inflammation-related genes; meanwhile, vitamin E can reduce some of the effects caused by NEFAs. This result may suggest that vitamin E can assist bovine PBLs in resisting the immune suppression caused by an NEB during the transition period.

Targeted Drug Nanodelivery and Immunotherapy for Combating Tumor Resistance.

Chemotherapy resistance is a common cause of tumor treatment failure. Various molecular responses, such as increased expression of efflux transporter proteins, including Pglycoprotein (P-gp), changes in the tumor microenvironment (TME), the role of platelets, and the effects of cancer stem cells (CSCs), can lead to drug resistance. Through extensive research on the mechanisms of drug resistance, more effective anti-resistance drugs and therapeutic approaches are being developed. This review explores drug resistance mechanisms and summarizes relevant anti-resistance drugs. In addition, due to the therapeutic limitations of the aforementioned treatments, new advances in nanocarrier-based combination immunotherapy to address the challenge of drug resistance have been described. Nanocarriers combined with immunotherapy can not only target tumor sites for targeted drug release but also modulate the autoimmune system and enhance immune efficacy, thereby overcoming tumor drug resistance. This review suggests new strategies for overcoming tumor drug resistance and is expected to inform tumor treatment and prognosis.

Visible Light-Catalyzed Reactions of Polysulfide (DBSPS) with Aryldiazonium.

A visible light-catalyzed radical coupling reaction of polysulfide reagents with aryldiazonium was developed, which gave thiosulfonates under mild conditions. In this reaction, the thiosulfonates were isolated in good yields with a broad tolerance to functional groups. And the synthesis of diaryl monosulfides were achieved through a step-by-step reaction of two molecular aryldiazonium with DBSPS, where the sulfur source was provided by DBSPS. It was worth noting that the reaction of this monosulfides could also be achieved by a one pot two-step process. The described polysulfide reagents were able to produce three new radicals: sulfonyl radicals, sulfur-sulfonyl radicals and sulfur-sulfur-sulfonyl radicals.

Identification and validation of the clinical prediction model and biomarkers based on chromatin regulators in colon cancer by integrated analysis of bulk- and single-cell RNA sequencing data.

Background: Chromatin regulators (CRs) are implicated in the development of cancer, but a comprehensive investigation of their role in colon adenocarcinoma (COAD) is inadequate. The purpose of this study is to find CRs that can provide recommendations for clinical diagnosis and treatment, and to explore the reasons why they serve as critical CRs. Methods: We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-Expression Network Analysis (WGCNA) screened tumor-associated CRs. LASSO-Cox regression was used to construct the model and to screen key CRs together with support vector machine (SVM), the univariate Cox regression. We used single-cell data to explore the expression of CRs in cells and their communication. Immune infiltration, immune checkpoints, mutation, methylation, and drug sensitivity analyses were performed. Gene expression was verified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Pan-cancer analysis was used to explore the importance of hub CRs. Results: We finally obtained 32 tumor-associated CRs. The prognostic model was constructed based on RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, and EYA2 by the LASSO-Cox regression. Single-cell data revealed that the model was immune-related. Combined with immune infiltration analysis, immune checkpoint analysis, and tumor immune dysfunction and exclusion (TIDE) analysis, the low-score risk group had more immune cell infiltration and better immune response. Mutation and methylation analysis showed that multiple CRs may be mutated and methylated in colon cancer. Drug sensitivity analysis revealed that the low-risk group may be more sensitive to several drugs and PKM was associated with multiple drugs. Combined with machine learning, PKM is perhaps the most critical gene in CRs. Pan-cancer analysis showed that PKM plays a role in the prognosis of cancers. Conclusions: We developed a prognostic model for COAD based on CRs. Increased expression of the core gene PKM is linked with a poor prognosis in several malignancies.

"Cicada Out of the Shell" Deep Penetration and Blockage of the HSP90 Pathway by ROS-Responsive Supramolecular Gels to Augment Trimodal Synergistic Therapy.

Deep penetration and downregulation of heat shock protein (HSP) expression in multimodal synergistic therapy are promising approaches for curing cancer in clinical trials. However, free small-molecule drugs and most drug vehicles have a low delivery efficiency deep into the tumor owing to poor drug penetration and hypoxic conditions at the tumor site. In this study, the objective is to use reactive oxygen species (ROS)-responsive supramolecular gels co-loaded with the photosensitizer Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4) and functionalized tetrahedral DNA (TGSAs) (G@P/TGSAs) to enhance deep tissue and cell penetration and block the HSP90 pathway for chemo- photodynamic therapy (PDT) - photothermal therapy (PTT) trimodal synergistic therapy. The (G@P/TGSAs) are injected in situ into the tumor to release ZnPCS4 and TGSAs under high ROS concentrations originating from both the tumor and PDT. TGSAs penetrate deeply into tumor tissues and augment photothermal therapy by inhibiting the HSP90 pathway. Proteomics show that HSP-related proteins and molecular chaperones are inhibited/activated, inhibiting the HSP90 pathway. Simultaneously, the TGSA-regulated apoptotic pathway is activated. In vivo study demonstrates efficient tumor penetration and excellent trimodal synergistic therapy (45% tumor growth inhibition).

Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.