STAT5 phosphorylation plus minimal residual disease defines a novel risk classification in adult B-cell acute lymphoblastic leukaemia.

The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow-pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event-free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow-based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD-) and others as moderate-risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3-year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow-based risk classification by integrating pSTAT5 and MRD in favour of risk-guided treatment for B-ALL.

PASS-ALL study of paediatric-inspired versus adult chemotherapy regimens on survival of high-risk Philadelphia-negative B-cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation.

This PASS-ALL study was designed to explore the effect of paediatric-inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia (HR PH-ve B-cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo-HSCT). The PASS-ALL study is a multicentre, observational cohort study, and 143 patients with HR B-cell PH-ve ALL were enrolled from five centres-77 patients allocated in the paediatric-inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo-HSCT. Three-year leukaemia-free survival (LFS) in the paediatric-inspired cohort was 72.2% (95% CI 60.8%-83.6%) compared with 44.6% (95% CI 31.9%-57.3%; p = 0.001). Furthermore, time-to-positive minimal residual disease (TTP-MRD) post-HSCT was marked different, 3-year cumulative incidence of relapse was 25.9% (95% CI 15.8%-37.2%) in paediatric cohort and 45.4% (95% CI 40.0%-57.9%) in adult cohort (p = 0.026). Finally, the 3-year OS rate was 75.3% (95% CI 64.9%-85.7%) for the paediatric-inspired cohort and 64.1% (95% CI 51.8%-76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric-inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327-4.862, p = 0.005). Collectively, our data suggest that paediatric-inspired chemotherapy pre-HSCT results in deeper and durable MRD response reduces relapse post-HSCT and improves survival in HR B-cell PH-ve ALL patients with allo-HSCT.

Mutations of epigenetic modifier genes predict poor outcome in adult acute lymphoblastic leukemia.

Epigenetic modifier (EM) genes play important roles in the occurrence and progression of acute lymphoblastic leukemia (ALL). However, the prognostic significance of EM mutations in ALL has not yet been thoroughly investigated. This retrospective study included 205 adult patients with ALL engaged in a pediatric-type regimen. Based on targeted next-generation sequencing, they were divided into EM mutation group (EM-mut, n = 75) and EM wild-type group (EM-wt, n = 130). The EM-mut group showed a higher positive rate of minimal residual disease (MRD) on treatment day24 and before consolidation therapy (P = 0.026, 0.020). Multivariate Cox regression analysis showed that EM-mut was an independent adverse factor for overall survival (OS) and event-free survival (EFS) (HR = 2.123, 1.742; P = 0.009, 0.007). Survival analysis revealed that the OS and EFS rates were significantly lower in the EM-mut group than in the EM-wt group (3-year OS rate, 45.8% vs. 65.0%, P = 0.0041; 3-year EFS rate, 36.7% vs. 53.2%, P = 0.011). In conclusion, EM was frequently mutated in adult ALL and was characterized by poor response to induction therapy and inferior clinical outcomes.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Symptomatic plant viroid infections in phytopathogenic fungi.

Viroids are pathogenic agents that have a small, circular noncoding RNA genome. They have been found only in plant species; therefore, their infectivity and pathogenicity in other organisms remain largely unexplored. In this study, we investigate whether plant viroids can replicate and induce symptoms in filamentous fungi. Seven plant viroids representing viroid groups that replicate in either the nucleus or chloroplast of plant cells were inoculated to three plant pathogenic fungi, Cryphonectria parasitica, Valsa mali, and Fusarium graminearum By transfection of fungal spheroplasts with viroid RNA transcripts, each of the three, hop stunt viroid (HSVd), iresine 1 viroid, and avocado sunblotch viroid, can stably replicate in at least one of those fungi. The viroids are horizontally transmitted through hyphal anastomosis and vertically through conidia. HSVd infection severely debilitates the growth of V. mali but not that of the other two fungi, while in F. graminearum and C. parasitica, with deletion of dicer-like genes, the primary components of the RNA-silencing pathway, HSVd accumulation increases. We further demonstrate that HSVd can be bidirectionally transferred between F. graminearum and plants during infection. The viroids also efficiently infect fungi and induce disease symptoms when the viroid RNAs are exogenously applied to the fungal mycelia. These findings enhance our understanding of viroid replication, host range, and pathogenicity, and of their potential spread to other organisms in nature.

Effects of in-package atmospheric cold plasma treatment on the qualitative, metabolic and microbial stability of fresh-cut pears.

BACKGROUND: The greatest hurdle to commercial marketing of fresh-cut fruits and vegetables is limited shelf life due to microbial hazards and quality deterioration. Atmospheric cold plasma (ACP) is an emerging non-thermal technology with significant potential to improve the safety and storability of fresh products. The objective of this study was to evaluate the effects of ACP, generated in sealed packaging, on the qualitative, metabolic and microbial stability of fresh-cut pears during simulated cold storage. RESULTS: ACP treatments were effective in inhibiting the growth of mesophilic aerobic bacteria, yeast and mold, particularly CP3 (65 kV, 1 min), which could prolong shelf life to the greatest extent. While decontamination was not always associated with an increase in plasma intensity. Moreover, at 65 kV for 1 min, ACP treatment had the potential to retard respiration, and maintain organoleptic properties and other quality attributes. Additionally, peroxidase and pectin methylesterase (PME) activities were reduced immediately after treatments. These effects were dependent on treatment voltage and time, while a subsequent recovery in activity was only observed for PME. CONCLUSION: The results obtained from this study will contribute to an understanding of the effects of in-package ACP treatments on the storability and microbial safety of fresh-cut pears. This knowledge could be beneficial in reducing quality losses for fresh-cut pears and the preservation of other products. © 2021 Society of Chemical Industry.

Early T-Cell Precursor Leukemia Has a Higher Risk of Induction-Related Infection among T-Cell Acute Lymphoblastic Leukemia in Adult.

BACKGROUND: Infections are an important cause of morbidity and mortality for acute lymphoblastic leukemia (ALL). However, the reports regarding risk factors of induction-related infection are roughly unknown/limited in adult T-ALL during induction chemotherapy. METHODS: We performed a retrospective cohort study for the prevalence and risk predictors of induction-related infection among consecutive T-ALL patients (N = 97) enrolled in a PDT-ALL-LBL clinical trial. Of 97 patients with T-ALL enrolled in the trial, 46 were early T-cell precursor (ETP) ALL and 51 were non-ETP ALL. RESULTS: When compared with non-ETP, ETP ALL subtype was characterized with lower neutrophil count (1.35 × 109/L vs. 8.7 × 109/L, P < 0.001) and lower myeloid percentage in the bone marrow (13.35% vs. 35.31%, P = 0.007). Additionally, ETP ALL had longer neutropenia before diagnosis (P < 0.001), as well as during induction chemotherapy (P < 0.001). Notably, the ETP cohort experienced higher cumulative incidence of clinically documented infections (CDI; 33.33%, P = 0.001), microbiologically documented infections (MDI; 45.24%, P = 0.006), resistant infection (11.9%, P = 0.013), and mixed infection (21.43%, P = 0.003), respectively, than those of the non-ETP cohort. Furthermore, multivariable analysis revealed that T-ALL mixed infection was more likely related to chemotherapy response (OR, 0.025; 95% CI 0.127-0.64; P = 0.012) and identified myeloid percentage as a predictor associated with ETP-ALL mixed infection (OR, 0.915; 95% CI 0.843-0.993; P = 0.033), with ROC-defined cut-off value of 2.24% in ETP cohorts. CONCLUSIONS: Our data for the first time demonstrated that ETP-ALL characterized with impaired myelopoiesis were more susceptible to induction-related infection among T-ALL populations.

Complete appendiceal inversion with local high-grade intraepithelial neoplasia in an adult female: a case report.

BACKGROUND: Appendiceal inversion with neoplasia in adults is an extremely rare event with a reported incidence of < 0.01%. Preoperative diagnosis is very important for surgical treatment; however, it is very difficult to be exact. CASE PRESENTATION: The patient was a 60-year-old woman with complaints of intermittent abdominal pain. Computed tomography and colonoscopy revealed a cecal mass, which was diagnosed as a tubulovillous adenoma in the preoperative colonoscopic biopsy. At surgery, the appendix was found to be completely inverted into the cecum. The cecum was partially resected, and surgical pathology examination confirmed a tubulovillous adenoma of the appendix with local high-grade intraepithelial neoplasia. CONCLUSIONS: Although preoperative diagnosis of appendiceal inversion with neoplasia may be often difficult due to its non-specific symptoms, clinicians should consider this disease entity when they encounter an intraluminal protruding cecal mass without visualization of the normal appendix on CT and colonoscopy.

Genome-wide identification and comparative analysis of the cation proton antiporters family in pear and four other Rosaceae species.

The monovalent cation proton antiporters (CPAs) play essential roles in plant nutrition, development, and signal transduction by regulating ion and pH homeostasis of the cell. The CPAs of plants include the Na(+)/H(+) exchanger, K(+) efflux antiporter, and cation/H(+) exchanger families. However, currently, little is known about the CPA genes in Rosaceae species. In this study, 220 CPA genes were identified from five Rosaceae species (Pyrus bretschneideri, Malus domestica, Prunus persica, Fragaria vesca, and Prunus mume), and 53 of which came from P. bretschneideri. Phylogenetic, structure, collinearity, and gene expression analyses were conducted on the entire CPA genes of pear. Gene expression data showed that 35 and 37 CPA genes were expressed in pear fruit and pollen tubes, respectively. The transcript analysis of some CPA genes under abiotic stress conditions revealed that CPAs may play an important role in pollen tubes growth. The results presented here will be useful in improving understanding of the complexity of the CPA gene family and will promote functional characterization in future studies.

Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia.

Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.

Genomic characterization, phylogenetic comparison and differential expression of the cyclic nucleotide-gated channels gene family in pear (Pyrus bretchneideri Rehd.).

The cyclic nucleotide-gated channel (CNGC) family is involved in the uptake of various cations, such as Ca(2+), to regulate plant growth and respond to biotic and abiotic stresses. However, there is far less information about this family in woody plants such as pear. Here, we provided a genome-wide identification and analysis of the CNGC gene family in pear. Phylogenetic analysis showed that the 21 pear CNGC genes could be divided into five groups (I, II, III, IVA and IVB). The majority of gene duplications in pear appeared to have been caused by segmental duplication and occurred 32.94-39.14 million years ago. Evolutionary analysis showed that positive selection had driven the evolution of pear CNGCs. Motif analyses showed that Group I CNGCs generally contained 26 motifs, which was the greatest number of motifs in all CNGC groups. Among these, eight motifs were shared by each group, suggesting that these domains play a conservative role in CNGC activity. Tissue-specific expression analysis indicated that functional diversification of the duplicated CNGC genes was a major feature of long-term evolution. Our results also suggested that the P-S6 and PBC & hinge domains had co-evolved during the evolution. These results provide valuable information to increase our understanding of the function, evolution and expression analyses of the CNGC gene family in higher plants.

[Effects of surgical resection of pulmonary lesions to the relapse of pulmonary aspergillosis in allogeneic hematopoietic stem cell transplant recipients with invasive pulmonary aspergillosis].

OBJECTIVE: To explore the rate of breakthrough invasive pulmonary aspergillosis (IPA) in patients receiving surgical resection of pulmonary aspergillosis lesions prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was conducted between January 2007 and June 2014. A total of 16 patients were enrolled, who had persistent pulmonary lesions including cavity (diameter >2.0 cm) or mass with a history of IPA prior to allo-HSCT in Nanfang Hospital of Southern Medical University. Ten of the 16 patients underwent thoracoscopic surgery before transplantation, i. e. surgery group, the other 6 patients did not have surgery because of primary underlying diseases (non-complete remission) or multiple lesions i. e. non-surgery group. Secondary prophylactic agents were administrated based on treatment response to initial antigual therapy. The 1-year cumulative and breakthrough rate of IPA, the median time of secondary antifungal prophylaxis (SAP) and overall survival were compared between surgery and non-surgery groups. RESULTS: Within a median follow-up of 364 days after transplantation (range 73 to 400 days). The success rate of SAP was 15/16. The 1-year cumulative and breakthrough IPA were 0 and 0 in surgery group, compared with 3/6 and 1/6 in non-surgery group. The median duration of SAP in surgery group and non-surgery group was 95(74-134)days and 192.5 (56-280)days respectively, which was significantly shorter in surgery group (P=0.017). The overall survival between two groups was 8/10 and 4/6 (P=0.534). No discontinuation of SAP happened in both groups due to drug-related adverse events. CONCLUSIONS: In patients with persistent pulmonary IPA lesions, surgical resection followed by SAP might be effective to reduce breakthrough IPA after transplantation with short duration of prophylaxis.

Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation.

Refractory acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic stem cell transplantation. This study evaluated the immunomodulation effects of mesenchymal stromal cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. Forty-seven patients with refractory aGVHD were enrolled: 28 patients receiving MSC and 19 patients without MSC treatment. MSCs were given at a median dose of 1 × 10(6) cells/kg weekly until patients got complete response or received 8 doses of MSCs. After 125 doses of MSCs were administered, with a median of 4 doses (range, 2 to 8) per patient, overall response rate was 75% in the MSC group compared with 42.1% in the non-MSC group (P = .023). The incidence of cytomegalovirus, Epstein-Barr virus infections, and tumor relapse was not different between the 2 groups during aGVHD treatment and follow-up. The incidence and severity of chronic GVHD in the MSC group were lower than those in the non-MSC group (P = .045 and P = .005). The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T cells, the frequencies of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), and the levels of signal joint T cell-receptor excision DNA circles (sjTRECs) after MSCs treatment were higher than those pretreatment. MSC-treated patients exhibited higher Tregs frequencies and sjTRECs levels than those in the non-MSC group at 8 and 12 weeks after treatment. MSCs derived from bone marrow of a third-party donor are effective to refractory aGVHD. It might reduce the incidence and severity of chronic GVHD in aGVHD patients by improving thymic function and induction of Tregs but not increase the risks of infections and tumor relapse.

Mitochondrial dysfunction mediated by cytoplasmic acidification results in pollen tube growth cessation in Pyrus pyrifolia.

The length of pollen tubes grown in synthetic media is normally shorter than those grown in vivo. However, the mechanism(s) underlying the cessation of pollen tube growth under culture conditions remain(s) largely unknown. Here, we report a previously unknown correlation between vacuolar function and the cell's ability to sustain mitochondrial functions in pear pollen tubes. The pear pollen tubes in vitro grew slowly after 15 hours post-cultured (HPC) and nearly ceased growth at 18 HPC. There was increased malondialdehyde content and membrane ion leakage at 15 HPC compared with 12 HPC. Furthermore, cytoplasmic acidification mainly mediated by decreased vacuolar H(+)-ATPase [V-ATPase, Enzyme Commission (EC) 3.6.1.3] activity was observed in pollen tubes after 15 HPC, and this further resulted in mitochondrial dysfunction, including mitochondrial structure disruption, mitochondrial membrane potential collapse and decreases in both oxygen consumption and ATP production. Our findings suggest that vacuoles and mitochondria intimately linked in regulating pollen tube elongation.

Artesunate Induces SKM-1 Cells Apoptosis by Inhibiting Hyperactive ß-catenin Signaling Pathway.

INTRODUCTION: Artesunate (ART), a wildly used agent to treat severe malarial around the world, also has the power to inhibit growth of different types of tumor. However, the exact molecular mechanisms keep unknown. METHOD: In this study, we used myelodysplastic syndrome (MDS) cells (SKM-1 cells) with differential ART concentrations treatment at multiple time points to observe the subsequence cell function alteration and the possible involved pathway genes. RESULTS: We found that ART demonstrated the ability to inhibit proliferation and induce apoptosis in SKM-1 in a dose and time-dependent manner. Demethylase recovered CDH1 gene expression may be involved in the apoptosis process. The ß-catenin protein translocated from the nucleus and cytoplasm to the membrane result in inactivation of ß-catenin signaling pathway. CONCLUSION: Our findings provide a rational basis to develop ART as a useful therapeutic agent for the treatment of myelodysplastic syndromes.

Mesenchymal stem cells versus mesenchymal stem cells combined with cord blood for engraftment failure after autologous hematopoietic stem cell transplantation: a pilot prospective, open-label, randomized trial.

Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.

Antifungal agents for secondary prophylaxis based on response to initial antifungal therapy in allogeneic hematopoietic stem cell transplant recipients with prior pulmonary aspergillosis.

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation.

Apoplastic calmodulin promotes self-incompatibility pollen tube growth by enhancing calcium influx and reactive oxygen species concentration in Pyrus pyrifolia.

Calmodulin (CaM) has been associated with various physiological and developmental processes in plants, including pollen tube growth. In this study, we showed that CaM regulated the pear pollen tube growth in a concentration-dependent bi-phasic response. Using a whole-cell patch-clamp configuration, we showed that apoplastic CaM induced a hyperpolarization-activated calcium ion (Ca²âº) current, and anti-CaM largely inhibited this type of Ca²âº current. Moreover, upon anti-CaM treatment, the reactive oxygen species (ROS) concentration decreased and actin filaments depolymerized in the pollen tube. Interestingly, CaM could partially rescue the inhibition of self-incompatible pear pollen tube growth. This phenotype could be mediated by CaM-enhanced pollen plasma membrane Ca²âº current, tip-localized ROS concentration and stabilized actin filaments. These data indicated that Ca²âº, ROS and actin filaments were involved with CaM in regulating pollen tube growth and provide a potential way for overcoming pear self-incompatibility.

The S100 family is a prognostic biomarker and correlated with immune cell infiltration in pan-cancer.

BACKGROUND: The S100 protein family is a group of small molecular EF-hand calcium-binding proteins that play critical roles in various biological processes, including promotion of growth, metastasis and immune evasion of tumor. However, the potential roles of S100 protein family expression in tumor microenvironment (TME) cell infiltration in pan-cancer remain elusive. METHODS: Herein, we conducted a comprehensive assessment of the expression patterns of the S100 protein family in pan-cancer, meticulously examining their correlation with characteristics of TME cell infiltration. The S100 score was constructed to quantify S100 family expression patterns of individual tumors. RESULTS: The S100 family was a potent risk factor in many cancers. Clustering analysis based on the transcriptome patterns of S100 protein family identified two cancer clusters with distinct immunophenotypes and clinical characteristics. Cluster A, with lower S100 expression, exhibited lower immune infiltration, whereas, Cluster B, with higher S100 expression, featured higher immune infiltration. Interestingly, Cluster B had a poorer prognosis, likely due to an immune-excluded phenotype resulting from stromal activation. The analysis revealed robust enrichment of the TGFb and EMT pathways in the cohort exhibiting high S100 score, alongside a positive correlation between the S100 score and Treg levels, suggesting the manifestation of an immune-excluded phenotype in this group. Moreover, S100 families were associated with the prognosis of 22 different cancers and a noteworthy association was observed between high S100 score and an unfavorable response to anti-PD-1/L1 immunotherapy. Consistent findings across two independent immunotherapy cohorts substantiated the advantageous therapeutic outcomes and clinical benefits in patients displaying lower S100score. CONCLUSION: Our analysis demonstrated the role of S100 family in formation of TME diversity and complexity, enabling deeper cognition of TME infiltration characterization and the development of personalized immunotherapy strategies targeting S100 family for unique tumor types.