Signature construction and molecular subtype identification based on liver-specific genes for prediction of prognosis, immune activity, and anti-cancer drug sensitivity in hepatocellular carcinoma.

BACKGROUND: Liver specific genes (LSGs) are crucial for hepatocyte differentiation and maintaining normal liver function. A deep understanding of LSGs and their heterogeneity in hepatocellular carcinoma (HCC) is necessary to provide clues for HCC diagnosis, prognosis, and treatment. METHODS: The bulk and single-cell RNA-seq data of HCC were downloaded from TCGA, ICGC, and GEO databases. Through unsupervised cluster analysis, LSGs-based HCC subtypes were identified in TCGA-HCC samples. The prognostic effects of the subtypes were investigated with survival analyses. With GSVA and Wilcoxon test, the LSGs score, stemness score, aging score, immune score and stromal score of the samples were estimated and compared. The HCC subtype-specific genes were identified. The subtypes and their differences were validated in ICGC-HCC samples. LASSO regression analysis was used for key gene selection and risk model construction for HCC overall survival. The model performance was estimated and validated. The key genes were validated for their heterogeneities in HCC cell lines with quantitative real-time PCR and at single-cell level. Their dysregulations were investigated at protein level. Their correlations with HCC response to anti-cancer drugs were estimated in HCC cell lines. RESULTS: We identified three LSGs-based HCC subtypes with different prognosis, tumor stemness, and aging level. The C1 subtype with low LSGs score and high immune score presented a poor survival, while the C2 subtype with high LSGs score and immune score indicated an enduring survival. Although no significant survival difference between C2 and C3 HCCs was shown, the C2 HCCs presented higher immune score and stroma score. The HCC subtypes and their differences were confirmed in ICGC-HCC dataset. A five-gene prognostic signature for HCC survival was constructed. Its good performance was shown in both the training and validation datasets. The five genes presented significant heterogeneities in different HCC cell lines and hepatocyte subclusters. Their dysregulations were confirmed at protein level. Furthermore, their significant associations with HCC sensitivities to anti-cancer drugs were shown. CONCLUSIONS: LSGs-based HCC subtype classification and the five-gene risk model might provide useful clues not only for HCC stratification and risk prediction, but also for the development of more personalized therapies for effective HCC treatment.

Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis.

BACKGROUND AND AIM: The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. METHODS: There were 173 patients with AP, all of whom developed symptoms within 72 h; 102 individuals had onset symptoms within 48 h. The biomarkers were measured upon admission before determining the severity of AP. RESULTS: The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72 h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48 h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P < 0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein. CONCLUSION: In the initial 48 h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72 h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT + TM + t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.

Salvage radiotherapy strategy and its prognostic significance for patients with locoregional recurrent cervical cancer after radical hysterectomy: a multicenter retrospective 10-year analysis.

OBJECTIVE: We aimed to evaluate the clinical efficacy and prognostic significance of intensity-modulated radiotherapy (IMRT)-based salvage concurrent chemoradiotherapy (CCRT) for patients with locoregional recurrence cervical cancer after radical hysterectomy and evaluated two salvage radiotherapy modes-regional RT (involved-field RT combined with regional lymph nodes) and local RT (involved-field RT). METHODS: Patients were enrolled retrospectively from January 2011 to January 2022 in three medical centers. Clinical outcomes were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare the two RT groups. RESULTS: There were 72 patients underwent IMRT-based salvage CCRT. The 5-year overall survival and progression-free survival rates were 65.9% and 57.6%, respectively. Univariate analysis showed that patients with stump recurrence, a lower systemic inflammation response index (SIRI), only one metastatic lesion, and received regional RT had better prognosis than their counterparts. In multivariate analysis, recurrence site was the independent prognostic factor of OS, and SIRI was that of PFS. After PS matching, there were 15 patients each in the regional RT group and local RT group. The 5-year OS rate of regional RT group was better than that of local RT group (90.9 vs. 42.4, p = 0.021). However, there was no significant difference between them in terms of PFS rate (47.1 vs. 38.1, p = 0.195). CONCLUSION: Locoregional recurrent cervical cancer treated with IMRT-based salvage therapy has a good prognosis. Recurrence site and SIRI were independent prognostic factors. Regional RT may be a better option for patients with locoregional recurrent.

ZNF655 promotes the progression of hepatocellular carcinoma through PSMB8.

Hepatocellular carcinoma (HCC) is a type of liver cancer that is associated with high mortality rates. This study aims to investigate the role of ZNF655, a member of the zinc finger protein family, in the development of HCC. Immunohistochemical staining analysis was conducted to evaluate the expression of ZNF655 in HCC patient samples. Lentivirus-mediated ZNF655 knockdown was established in HCC cell lines (BEL-7402 and HCCLM3). The effects of ZNF655 on different aspects of HCC cell behavior such as proliferation, apoptosis, cycle, migration and tumor formation were examined. Downstream targets of ZNF655 in HCC were identified and verified through loss/gain-of-function experiments. Clinically, ZNF655 expression was elevated in HCC and increased with the severity of the disease. Functionally, inhibition of ZNF655 expression reduced the progression of HCC cells by decreasing proliferation, causing apoptosis, arresting cell cycle retention in G2, suppressing migration, and attenuating tumor formation in mice. Mechanistically, the proteasome subunit beta type-8 (PSMB8) was found to be co-expressed with ZNF655 in HCC, and PSMB8 knockdown weakened the promotion of ZNF655 overexpression on HCC. In summary, these findings suggest that ZNF655 promotes the progression of HCC through PSMB8, and inhibition of its expression may be a promising therapeutic target for HCC.

The value of right heart contrast echocardiography combined with migraine rating scale in evaluating the efficacy of patent foramen ovale closure.

OBJECTIVES: To investigate the clinical values of right heart contrast transthoracic echocardiography (cTTE) combined with migraine rating scale in evaluating the efficacy of patent foramen ovale (PFO) closure. METHODS: From January 2018 to December 2021, a total of 68 hospitalized patients, 21 males and 47 females, who were treated with transcatheter closure of PFO-induced migraine in the Heart Center of the First Affiliated Hospital of Tsinghua University were selected, with the age of 38.4 ± 11.9 years old. The changes of right heart contrast transthoracic echocardiography (cTTE), visual analogue pain score(VAS), headache impact test-6(HIT-6) and migraine disability assessment questionnaire(MIDAS) before and 6 months after PFO occlusion were compared. RESULTS: Pre-operative cTTE data show that 36 patients (52.9%) had moderate right-to-left shunt (RLS), and 32 patients (47.1%) had massive RLS. cTTE was reexamined 6 months after operation and 1 case in the moderate RLS group had minimal RLS, 2 cases in the large RLS group had minimal RLS, and no shunts were seen for the rest. The VAS, HIT-6 and MIDAS scores before and 6 months after the operation were 7.65 ± 1.39 vs. 1.28 ± 1.53, 70.78 ± 6.82 vs. 41.53 ± 6.07, and 30.60 ± 13.24 vs. 1.93 ± 3.87, respectively. All the indexes 6 months after the operation significantly improved compared with the preoperative baseline (P < 0.05). CONCLUSIONS: cTTE combined with migraine evaluation scale could be used as an objective index to evaluate the clinical effect of PFO occlusion.

CD5L-associated gene analyses highlight the dysregulations, prognostic effects, immune associations, and drug-sensitivity predicative potentials of LCAT and CDC20 in hepatocellular carcinoma.

BACKGROUND: The dysregulation of CD5L has been reported in hepatocellular carcinoma (HCC). However, its functions in HCC were controversial. In this study, we aimed to identify CD5L-associated pathways and markers and explore their values in HCC diagnosis, prognosis and treatment. METHODS: HCC datasets with gene expression profiles and clinical data in TCGA and ICGC were downloaded. The immune/stroma cell infiltrations were estimated with xCell. CD5L-associated pathways and CD5L-associated genes (CD5L-AGs) were identified with gene expression comparisons and gene set enrichment analysis (GSEA). Cox regression, Kaplan-Meier survival analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis were performed. The correlations of the key genes with immune/stroma infiltrations, immunoregulators, and anti-cancer drug sensitivities in HCC were investigated. At protein level, the key genes dysregulations, their correlations and prognostic values were validated in clinical proteomic tumor analysis consortium (CPTAC) database. Serum CD5L and LCAT activity in 50 HCC and 30 normal samples were evaluated and compared. The correlations of serum LCAT activity with alpha-fetoprotein (AFP), albumin (ALB) and high-density lipoprotein (HDL) in HCC were also investigated. RESULTS: Through systemic analyses, 14 CD5L-associated biological pathways, 256 CD5L-AGs and 28 CD5L-associated prognostic and diagnostic genes (CD5L-APDGs) were identified. A risk model consisting of LCAT and CDC20 was constructed for HCC overall survival (OS), which could discriminate HCC OS status effectively in both the training and the validation sets. CD5L, LCAT and CDC20 were shown to be significantly correlated with immune/stroma cell infiltrations, immunoregulators and 31 anti-cancer drug sensitivities in HCC. At protein level, the dysregulations of CD5L, LCAT and CDC20 were confirmed. LCAT and CDC20 were shown to be significantly correlated with proliferation marker MKI67. In serum, no significance of CD5L was shown. However, the lower activity of LCAT in HCC serum was obvious, as well as its significant positive correlations ALB and HDL concentrations. CONCLUSIONS: CD5L, LCAT and CDC20 were dysregulated in HCC both at mRNA and protein levels. The LCAT-CDC20 signature might be new predicator for HCC OS. The associations of the three genes with HCC microenvironment and anti-cancer drug sensitivities would provide new clues for HCC immunotherapy and chemotherapy.

Knockdown of POLQ interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration.

BACKGROUND: DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated. METHODS: In the present study, both the data collected from the Cancer Genome Atlas (TCGA) and our group's results showed higher POLQ expression in HCC tissues than the para-cancerous tissues, which was associated with higher malignancy and poor prognosis. POLQ knockdown HCC cell model (shPOLQ) was constructed along with the corresponding negative control (shCtrl) through lentivirus infection for loss-of-function study. RESULTS: We found that, upon knockdown of POLQ, the proliferation and migration of HCC cells decreased and apoptosis percentage increased. Moreover, the percentage of cells in G2 phase significantly increased in shPOLQ group compared with shCtrl group. Xenografts in mice grafted with shPOLQ cells grew much slower than that transplanted with shCtrl cells, and expressed lower Ki67 level. Furthermore, an apoptosis-related signaling array was used to explore the involvement of downstream signaling pathways, suggesting the enhanced phosphorylation of HSP27 and JNK, and the de-activation of mTOR, PRAS40, ERK1/2 and STAT3 pathways. CONCLUSIONS: Collectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC.

Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox-LDL-induced endothelial dysfunction in atherosclerosis by functioning as a miR-876-3p sponge.

Circular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK-8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell-cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR-876-3p, CCND2 and SUCNR1 were assayed by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR-876-3p axis on cell proliferation, migration and tube formation. Oxidized low-density lipoprotein inhibited cell viability and cell-cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR-876-3p was upregulated in AS patients and ox-LDL-treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox-LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR-876-3p and miR-876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR-876-3p. Meanwhile, miR-876-3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR-876-3p also alleviated the ox-LDL-induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR-876-3p. The protective effects of circ_0093887 on HAECs from ox-LDL were also ​alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox-LDL-induced inflammatory and apoptotic damages by targeting the miR-876-3p/CCND2 or miR-876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.

Effect of cerium oxide doping on the performance of CaO-based sorbents during calcium looping cycles.

A series of CaO-based sorbents were synthesized through a sol-gel method and doped with different amounts of CeO2. The sorbent with a Ca/Ce molar ratio of 15:1 showed an excellent absorption capacity (0.59 gCO2/g sorbent) and a remarkable cycle durability (up to 18 cycles). The admirable capture performance of CaCe-15 was ascribed to its special morphology formed by the doping of CeO2 and the well-distributed CeO2 particles. The sorbents doped with CeO2 possessed a loose shell-connected cross-linking structure, which was beneficial for the contact between CaO and CO2. CaO and CeO2 were dispersed homogeneously, and the existence of CeO2 also decreased the grain size of CaO. The well-dispersed CeO2, which could act as a barrier, effectively prevented the CaO crystallite from growing and sintering, thus the sorbent exhibited outstanding stability. The doping of CeO2 also improved the carbonation rate of the sorbent, resulting in a high capacity in a short period of time.

GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signaling pathway.

G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and regulate various physiological and pathological processes. Despite extensive studies, the roles of GPCRs in mouse embryonic stem cells (mESCs) remain poorly understood. Here, we show that GPR160, a class A member of GPCRs, is dramatically downregulated concurrent with mESC differentiation into embryoid bodies in vitro. Knockdown of Gpr160 leads to downregulation of the expression of pluripotency-associated transcription factors and upregulation of the expression of lineage markers, accompanying with the arrest of the mESC cell-cycle in the G0/G1 phase. RNA-seq analysis shows that GPR160 participates in the JAK/STAT signaling pathway crucial for maintaining ESC stemness, and the knockdown of Gpr160 results in the downregulation of STAT3 phosphorylation level, which in turn is partially rescued by colivelin, a STAT3 activator. Consistent with these observations, GPR160 physically interacts with JAK1, and cooperates with leukemia inhibitory factor receptor (LIFR) and gp130 to activate the STAT3 pathway. In summary, our results suggest that GPR160 regulates mESC self-renewal and pluripotency by interacting with the JAK1-LIFR-gp130 complex to mediate the JAK1/STAT3 signaling pathway.

Study of a precise treatment protocol for patients with consciousness disorders based on the brain network analysis of functional magnetic resonance imaging.

Objective: How to conduct objective and accurate individualized assessments of patients with disorders of consciousness (DOC) and carry out precision rehabilitation treatment technology is a major rehabilitation problem that needs to be solved urgently. Methods: In this study, a multi-layer brain network was constructed based on functional magnetic resonance imaging (fMRI) to analyze the structural and functional brain networks of patients with DOC at different levels and to find regulatory targets (imaging markers) with recovery potential for DOC. Then repeated transcranial magnetic stimulation (rTMS) was performed in DOC patients to clinically validate. Results: The brain network connectivity of DOC patients with different consciousness states is different, and the most obvious brain regions appeared in the olfactory cortex and precuneus. rTMS stimulation could effectively improve the consciousness level of DOC patients and stimulate the occipital lobe (specific regions found in this study) and the dorsolateral prefrontal cortex (DLPFC), and both parts had a good consciousness recovery effect. Conclusion: In clinical work, personalized stimulation regimen treatment combined with the brain network characteristics of DOC patients can improve the treatment effect.

Lipid Metabolism Traits Mediate the Effect of Psoriasis on Myocardial Infarction Risk: A Two-Step Mendelian Randomization Study.

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005-1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010-1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002-1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014-1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients.

Facial Merkel cell carcinoma in a patient with diabetes and hepatitis B: A case report.

BACKGROUND: Patients with chronic inflammatory disorders are at a higher risk of developing aggressive Merkel cell carcinoma (MCC). Diabetes is a common chronic inflammatory disease that is possibly associated with MCC; however, there are still no reports on the association between hepatitis B virus (HBV) infection and MCC. Whether there is an association between these three diseases and the specific mechanisms behind their effects is worth further research in the future. CASE SUMMARY: We herein report a rare case of MCC with extracutaneous and nodal invasion in an Asian individual with type 2 diabetes mellitus and chronic HBV infection, but no immunosuppression or other malignancies. Such cases are uncommon and have rarely been reported in the literature. A 56-year-old Asian male presented with a significant mass on his right cheek and underwent extensive resection combined with parotidectomy, neck lymphadenectomy, and split-thickness skin grafting. Based on the histopathological findings, a diagnosis of MCC involving the adipose tissue, muscle, nerve, and parotid gland with lymphovascular invasion was made. Subsequently, he received radiotherapy with no adverse reactions. CONCLUSION: MCC is a rare, aggressive skin cancer with frequent local recurrence, nodal invasion, and metastasis, which usually arises in older people of the white race. Patients with chronic inflammatory disorders are at a higher risk of developing aggressive MCC. The diagnosis can be confirmed with histology and immunohistochemistry. For localized MCC, surgery is the preferred treatment option. However, for advanced MCC, radiotherapy and chemotherapy have proven to be effective. In cases where chemotherapy is not effective or in the advanced stages of MCC, immune therapy plays an important role in treatment. As with any rare disease, the management of MCC remains an enormous challenge for clinicians; thus, follow-up should be individualized and future progress needs multidisciplinary collaborative efforts. Furthermore, physicians should include MCC in their list of possible diagnoses when they come across painless, rapidly growing lesions, particularly in patients with chronic HBV infection or diabetes, as these patients are more susceptible to the development of this condition and it tends to be more aggressive in them.

Tartary Buckwheat Starch Modified with Octenyl Succinic Anhydride for Stabilization of Pickering Nanoemulsions.

In this study, Tartary buckwheat starch was modified to different degrees of substitution (DS) with octenyl succinate anhydride (OS-TBS) in order to explore its potential for stabilizing Pickering nanoemulsions. OS-TBS was prepared by reacting Tartary buckwheat starch with 3, 5 or 7% (w/v) octenyl succinate in an alkaline aqueous solution at pH 8.5. Fourier-transform infrared spectroscopy gave peaks at 1726 cm-1 (C=O) and 1573 cm-1 (RCOO-), indicating the formation of OS-TBS. We further studied the physicochemical properties of the modified starch as well as its emulsification capacity. As the DS with octenyl succinate anhydride increased, the amylose content and gelatinization temperature of the OS-TBS decreased, while its solubility increased. In contrast to the original Tartary buckwheat starch, OS-TBS showed higher surface hydrophobicity, and its particles were more uniform in size and its emulsification stability was better. Higher DS with octenyl succinate led to better emulsification. OS-TBS efficiently stabilized O/W Pickering nanoemulsions and the average particle size of the emulsion was maintained at 300-400 nm for nanodroplets. Taken together, these results suggest that OS-TBS might serve as an excellent stabilizer for nanoscale Pickering emulsions. This study may suggest and expand the use of Tartary buckwheat starch in nanoscale Pickering emulsions in various industrial processes.

A Chronic Multiple Site of Scrofuloderma: Is It Reactivation or Treatment Failure of Tuberculosis?

We report a case of 32-year-old patient who presented with painless erythematous plaque gradually ulcerated for 9 years. He had a history of pulmonary tuberculosis 12 years ago and was cured by the treatment of 2HRZE/4HR. The laboratory examination of t-spot and PPD skin test was positive. Histopathology examinations of left cervical lymph node as well as skin revealed granulomatous inflammation with caseous necrosis. A diagnosis of scrofuloderma was made. Negative sputum culture and chest CT scan results excluded pulmonary tuberculosis. The patient was treated with a standard antituberculosis therapy and recovered well after 5 months' follow-up. Scrofuloderma is a rare manifestation of mycobacterial infection. Early diagnosis and treatment are very important.

T cell-derived exosomes in tumor immune modulation and immunotherapy.

Exosomes are nanoscale vesicles secreted by most cells and have a phospholipid bilayer structure. Exosomes contain DNA, small RNA, proteins, and other substances that can carry proteins and nucleic acids and participate in communication between cells. T cells are an indispensable part of adaptive immunity, and the functions of T cell-derived exosomes have been widely studied. In the more than three decades since the discovery of exosomes, several studies have revealed that T cell-derived exosomes play a novel role in cell-to-cell signaling, especially in the tumor immune response. In this review, we discuss the function of exosomes derived from different T cell subsets, explore applications in tumor immunotherapy, and consider the associated challenges.

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer.

This study evaluated the efficacy and safety of cisplatin and nedaplatin in three-week doublet agent concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC). We retrospectively enrolled patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020. Clinical outcomes were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare cisplatin plus docetaxel group and nedaplatin plus docetaxel group. A total of 295 patients were included. The 5-year overall survival rate (OS) and progression free survival rate (PFS) were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. There were no significant differences in objective response rates (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs 69.8, p = 0.066), PFS rate (90.8 vs 72.4, p = 0.166), and toxicity between the two groups. Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, cisplatin group has a trend of better prognosis, suggesting that cisplatin is preferred and nedaplatin can be considered for replacement when cisplatin is intolerant.

Legume-specific SnRK1 promotes malate supply to bacteroids for symbiotic nitrogen fixation.

Nodulation is an energy-expensive behavior driven by legumes by providing carbon sources to bacteroids and obtaining nitrogen sources in return. The energy sensor sucrose nonfermenting 1-related protein kinase 1 (SnRK1) is the hub of energy regulation in eukaryotes. However, the molecular mechanism by which SnRK1 coordinates the allocation of energy and substances during symbiotic nitrogen fixation (SNF) remains unknown. In this study, we identified the novel legume-specific SnRK1α4, a member of the SnRK1 family that positively regulates SNF. Phenotypic analysis showed that nodule size and nitrogenase activity increased in SnRK1α4-overexpressing plants and decreased significantly in snrk1α4 mutants. We demonstrated that a key upstream kinase involved in nodulation, Does Not Make Infection 2 (DMI2), can phosphorylate SnRK1α4 at Thr175 to cause its activation. Further evidence clarified that SnRK1α4 phosphorylates the malate dehydrogenases MDH1/2 to promote malate production in the cytoplasm, supplying carbon sources to bacteroids. Therefore, our findings reveal an essential role of the DMI2-SnRK1α4-MDH pathway in supplying carbon sources to bacteroids for SNF and provide a new module for constructing cereal crops with SNF.

Fabrication of Poly (Trans-3-(3-Pyridyl)Acrylic Acid)/Multi-Walled Carbon Nanotubes Membrane for Electrochemically Simultaneously Detecting Catechol and Hydroquinone.

Herein, conductive polymer membrane with excellent performance was successfully fabricated by integrating carboxylated multi-walled carbon nanotubes (MWCNTs) and poly (trans-3-(3-pyridyl) acrylic acid) (PPAA) film. The drop-casting method was employed to coated MWCNTs on the glassy carbon electrode (GCE) surface, and PPAA was then electropolymerized onto the surface of the MWCNTs/GCE in order to form PPAA-MWCNTs membrane. This enables the verification of the excellent performances of proposed membrane by electrochemically determining catechol (CC) and hydroquinone (HQ) as the model. Cyclic voltammetry experiments showed that the proposed membrane exhibited an obvious electrocatalytic effect on CC and HQ, owing to the synergistic effect of PPAA and MWCNTs. Differential pulse voltammetry was adopted for simultaneous detection purposes, and an increased electrochemical responded to CC and HQ. A concentration increase was found in the range of 1.0 × 10-6 mol/L~1.0 × 10-4 mol/L, and it exhibited a good linear relationship with satisfactory detection limits of 3.17 × 10-7 mol/L for CC and 2.03 × 10-7 mol/L for HQ (S/N = 3). Additionally, this constructed membrane showed good reproducibility and stability. The final electrode was successfully applied to analyze CC and HQ in actual water samples, and it obtained robust recovery for CC with 95.2% and 98.5%, and for HQ with 97.0% and 97.3%. Overall, the constructed membrane can potentially be a good candidate for constructing electrochemical sensors in environmental analysis.