Ruxolitinib plus basiliximab therapy for steroid-refractory acute graft-versus-host disease in unrelated cord blood transplantation: a large-scale study.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is a major cause of mortality after allogeneic stem cell transplantation (allo-HSCT). We aimed to evaluate the effectiveness and safety of ruxolitinib plus basiliximab for treating SR-aGVHD after unrelated cord blood transplantation (UCBT). Among the 1154 patients with hematological malignancies who underwent UCBT between February 2014 and May 2022, 198 patients with grade II to IV SR-aGVHD were enrolled, 112 of whom were treated with basiliximab alone (basiliximab group) and 86 of whom received basiliximab plus ruxolitinib (combined therapy group). The combined therapy group demonstrated a significantly higher complete response rate (CRR) on day 28 (36.0%) than did the basiliximab group (12.5%, P < 0.001). SR-aGVHD patients were further stratified into standard-risk and high-risk groups using the refined Minnesota aGVHD risk score. For standard-risk patients, combined therapy significantly improved the CRR (51.1% versus 13.6%, P < 0.001) and 3-year overall survival (74.5% versus 52.4%, P = 0.033). However, high-risk patients did not exhibit the same benefits. Compared with basiliximab monotherapy, ruxolitinib plus basiliximab therapy was an effective therapy for patients with standard-risk SR-aGVHD following UCBT. The effectiveness of combined therapy in high-risk patients was not apparent, indicating the need for other treatments.

Prognostic value of GARS in bladder cancer and its role in the tumor microenvironment.

Background: Bladder cancer (BC), as a common type of cancer, has a poor prognosis, also some common invasive prognostic or therapeutic markers are difficult to obtain, which makes further treatment of BC difficult. Glycyl-tRNA synthetase (GARS), as one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids, has been identified as a target in many diseases, including tumors. Methods: Bioassay analysis revealed that GARS was in high expression in most cancer tissues. The expression of GARS gene in BC tissues could assess the prognosis of BC patients, and the expression in urinary extracellular vesicles (uEVs) of patients was positively correlated with the expression in tissues. In addition to this, we analyzed GARS-related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. In vivo and vitro tumorigenic experiments were performed to validate the function of GARS. Single-cell data were used to further analyze its role in the microenvironment. Results: In our study, we found that GARS was highly expressed in 30 cancer tissues including BC, and high GARS expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low GARS groups by enrichment analysis, and identified the biological signaling pathways that were mainly enriched for their functions, and found that the enrichment was found in immune-related signaling pathways and regulation of cell-cell adhesion. Then we found that GARS was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the GARS-high group. Besides, we found that GARS was enriched in myofibroblasts in the tumor microenvironment, and the enrichment was positively correlated with epithelial-mesenchymal transition (EMT)-related genes. This study also showed a positive correlation between GARS and BC RNA stemness. Patients in the GARS-high group had considerably higher rates of P53 and Titin (TTN) mutations than those in the GARS-low group. Drug Sensitivity analysis screened for drugs that were more sensitive to GARS-high patients. Further, we found that knockdown of GARS significantly inhibited the proliferation, migration and invasion ability both in vivo and in vitro. Finally, we found that in patients with high GARS the expression in uEVs was also at a high level. Conclusions: In summary, this study provided evidence that GARS can be used as a prognostic and therapeutic marker for BC, we can detect GARS in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.

Reconstituted CD74+ NK cells trigger chronic graft versus host disease after allogeneic bone marrow transplantation.

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear. Here, we found allogeneic recipients showed obvious pulmonary cGVHD. Surprisingly, deletion of reconstituted NK cells resulted in maximal relief of pulmonary cGVHD. Mechanistically, reconstituted NK cells with donor profiles modulated the pulmonary inflammatory microenvironment to trigger cGVHD. Reconstituted NK cells secreted IFN-γ and TNF-α to induce CXCL10 production by epithelial cells, which recruited macrophages and CD4+ T cells to the lungs. Then macrophages and CD4+ T cells were activated by the inflammatory microenvironment, thereby mediating lung injury. Through assessment of differences in cellular energy, we found that CD74+ NK cells with high mitochondrial potential and pro-inflammatory activity triggered pulmonary cGVHD. Furthermore, targeted elimination of CD74+ NK cells using the anti-CD74 antibody significantly alleviated pulmonary cGVHD but preserved the CD74- NK cells to exert graft-versus-leukemia (GVL) effects. Data from human samples corroborated our findings in mouse models. Collectively, our results reveal that reconstituted CD74+ NK cells trigger pulmonary cGVHD and suggest that administration of CD74 antibody was a potential therapeutic for patients with cGVHD.

Changes in planta K nutrient content altered the interaction pattern between Nicotiana benthamiana and Alternaria longipes.

Potassium (K) fertilisation has frequently been shown to enhance plant resistance against pathogens, though the mechanisms remain elusive. This study investigates the interaction dynamics between Nicotiana benthamiana and the pathogen Alternaria longipes under different planta K levels. On the host side, adding K activated the expressions of three NLR (nucleotide-binding domain and leucine-rich repeat-containing proteins) resistance genes, including NbRPM1, NbR1B23 and NbNBS12. Silencing these NLRs attenuated resistance in high-K (HK, 40.8 g/kg) plant, whereas their overexpression strengthened resistance in low-K (LK, 23.9 g/kg) plant. Typically, these NLRs mainly strengthened plant resistance via promoting the expression of pathogenesis-related genes (PRs), ROS burst and synthesis of antifungal metabolites in HK plant. On the pathogen side, the expression of effectors HKCSP1, HKCSP2 and LKCSP were shown to be related to planta K content. A. longipes mainly expressed effectors HKCSP1 and HKCSP2 in HK plant to interfere host resistance. HKCSP1 physically interacted with NbRPM1 to promote the degradation of NbRPM1, then attenuated related resistance in HK N. benthamiana. Meanwhile, HKCSP2 directly interacted with NbPR5 to suppress resistance in HK plant. In LK plant, A. longipes mainly deployed LKCSP that interacted with NbR1B23 to interfere reduce resistance in N. benthamiana. Overall, our research insights that both pathogen and host mobilise distinct strategies to outcompete each other during interactions in different K nutrient environments.

Adsorption of Asphaltenes at Model Oil/Brine Interface: Influence of Solvent Polarity.

With the exploitation of heavy oil worldwide, the influence of asphaltene aggregation in the oil phase on the stability of crude oil emulsion has been paid more and more attention. Under this background, the effects of solvent polarity on model oil/brine water interfacial properties and emulsion stability are investigated in this study. It is demonstrated that there is a critical asphaltene concentration for the formation of a stable emulsion. This critical concentration is then found to increase from 80 to 500 ppm with the mixing ratio of methylnaphthalene to n-decane changed from 2:3 to 7:3. The dynamic light scattering experiment shows that the average aggregate size increases abruptly from 132.8 to 261.1 nm at 2:3 mixing ratio of methylnaphthalene to n-decane once the asphaltenes are added to above the critical concentration. Accordingly, the diffusion coefficient of the asphaltenes decreases sharply from 4.36 × 10-12 to 5.68 × 10-13 m2/s. Similar conclusions are also found for the other mixing ratios of 1:1, 3:2, and 7:3. Besides, the aggregation degree of asphaltenes weakens, and the diffusion coefficient enlarges at the same asphaltene concentration with the enhancement of the solvent polarity. Further, the interfacial experiments manifest that the equilibrium interfacial dilation modulus decreases from 38.42 to 23.65 mN/m with the mixing ratio of methylnaphthalene to n-decane increased from 2:3 to 7:3. It can thus be inferred that the structural strength of the interfacial film decreases with the enhancement of the solvent polarity.

Genome comparisons reveal accessory genes crucial for the evolution of apple Glomerella leaf spot pathogenicity in Colletotrichum fungi.

Apple Glomerella leaf spot (GLS) is an emerging fungal disease caused by Colletotrichum fructicola and other Colletotrichum species. These species are polyphyletic and it is currently unknown how these pathogens convergently evolved to infect apple. We generated chromosome-level genome assemblies of a GLS-adapted isolate and a non-adapted isolate in C. fructicola using long-read sequencing. Additionally, we resequenced 17 C. fructicola and C. aenigma isolates varying in GLS pathogenicity using short-read sequencing. Genome comparisons revealed a conserved bipartite genome architecture involving minichromosomes (accessory chromosomes) shared by C. fructicola and other closely related species within the C. gloeosporioides species complex. Moreover, two repeat-rich genomic regions (1.61 Mb in total) were specifically conserved among GLS-pathogenic isolates in C. fructicola and C. aenigma. Single-gene deletion of 10 accessory genes within the GLS-specific regions of C. fructicola identified three that were essential for GLS pathogenicity. These genes encoded a putative non-ribosomal peptide synthetase, a flavin-binding monooxygenase and a small protein with unknown function. These results highlight the crucial role accessory genes play in the evolution of Colletotrichum pathogenicity and imply the significance of an unidentified secondary metabolite in GLS pathogenesis.

Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation.

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance.

This study aimed to explore the involvement of Transmembrane and coiled-coil domains 1 (TMCO1) in ovarian cancer progression and its regulatory mechanisms in cisplatin resistance. Using the GEPIA database, we analyzed TMCO1 expression in ovarian cancer and normal tissues. In a cohort of 99 ovarian cancer patients, immunohistochemistry and immunofluorescence were employed to assess TMCO1 expression in tumor and adjacent tissues, correlating findings with clinical and pathological characteristics. TMCO1 overexpression and knockout cell models were constructed, and their impact on non-cisplatin-resistant (SK-OV-3) and cisplatin-resistant (SK-OV-3-CDDP) ovarian cancer cells was investigated through cloning, wound healing, Fluo 4, and Transwell experiments. Knocking down CALR and VDAC1 was performed to examine their effects on TMCO1, cell proliferation, and malignant markers. Subcutaneous tumor models in nude mice elucidated the in vivo role of TMCO1 in tumor growth. Expression levels of CALR, VDAC1, angiogenesis indicators (CD34), and epithelial-mesenchymal transition (EMT) markers were evaluated. TMCO1 expression in ovarian cancer tissue significantly differed from normal tissue, correlating with survival rates. TMCO1 overexpression was associated with lymph node metastases, late FIGO stage, and larger tumors. TMCO1 promoted proliferation, calcium ion elevation, cytoskeletal remodeling, and metastasis in SK-OV-3 and SK-OV-3-CDDP cells, upregulating VDAC1, CALR, Vimentin, N-cadherin, ß-catenin, and downregulating E-cadherin. Silencing TMCO1 inhibited cell growth, proliferation, and angiogenesis in vivo, suppressing the expression of CALR, VDAC1, Vimentin, N-cadherin, and ß-catenin. Overall, this study highlighted TMCO1 as a crucial regulator in ovarian cancer progression, influencing VDAC1 through CALR and impacting diverse cellular processes, offering potential as a targeted therapeutic strategy for ovarian cancer.

Major quality regulation network of flavonoid synthesis governing the bioactivity of black wolfberry.

Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear. Presently, we compared the bioactivity of black wolfberry from five production regions. Multi-omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods. Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti-inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol-3-O-rutinoside (K3R) and Quercetin-3-O-rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32-regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32-regulated flavonoid biosynthesis was light-responsive, showing the importance of light intensity for the medicinal quality of black wolfberry. Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high-quality black wolfberry.

Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

An ensemble learning-based feature selection algorithm for identification of biomarkers of renal cell carcinoma.

Feature selection plays a crucial role in classification tasks as part of the data preprocessing process. Effective feature selection can improve the robustness and interpretability of learning algorithms, and accelerate model learning. However, traditional statistical methods for feature selection are no longer practical in the context of high-dimensional data due to the computationally complex. Ensemble learning, a prominent learning method in machine learning, has demonstrated exceptional performance, particularly in classification problems. To address the issue, we propose a three-stage feature selection algorithm framework for high-dimensional data based on ensemble learning (EFS-GINI). Firstly, highly linearly correlated features are eliminated using the Spearman coefficient. Then, a feature selector based on the F-test is employed for the first stage selection. For the second stage, four feature subsets are formed using mutual information (MI), ReliefF, SURF, and SURF* filters in parallel. The third stage involves feature selection using a combinator based on GINI coefficient. Finally, a soft voting approach is proposed to employ for classification, including decision tree, naive Bayes, support vector machine (SVM), k-nearest neighbors (KNN) and random forest classifiers. To demonstrate the effectiveness and efficiency of the proposed algorithm, eight high-dimensional datasets are used and five feature selection methods are employed to compare with our proposed algorithm. Experimental results show that our method effectively enhances the accuracy and speed of feature selection. Moreover, to explore the biological significance of the proposed algorithm, we apply it on the renal cell carcinoma dataset GSE40435 from the Gene Expression Omnibus database. Two feature genes, NOP2 and NSUN5, are selected by our proposed algorithm. They are directly involved in regulating m5c RNA modification, which reveals the biological importance of EFS-GINI. Through bioinformatics analysis, we shows that m5C-related genes play an important role in the occurrence and progression of renal cell carcinoma, and are expected to become an important marker to predict the prognosis of patients.

Upfront Umbilical Cord Blood Transplantation Versus Immunosuppressive Therapy for Pediatric Patients With Idiopathic Severe Aplastic Anemia.

Umbilical cord blood transplantation (UCBT) has been rarely reported as a first-line treatment for idiopathic severe aplastic anemia (SAA) patients lacking HLA-matched sibling donors (MSD). Our study aimed to compare the clinical outcomes of pediatric SAA patients who received UCBT and immunosuppressive therapy (IST) upfront. A retrospective analysis was performed on 43 consecutive patients who received frontline IST (n = 17) or UCBT (n = 26) between July 2017 and April 2022. The 3-year overall survival (OS) was comparable between the UCBT and IST groups (96.2% versus 100%, P = .419), while the 3-year event-free survival (EFS) was significantly better in the former than in the latter (88.5% versus 58.8%, P = .048). In the UCBT group, 24 patients achieved successful engraftment, 2 patients developed severe acute graft-versus-host disease (aGVHD), no extensive chronic GVHD (cGVHD), and a high GVHD-free, failure-free survival (GFFS) of 84.6% at 3 years. After 1 year of treatment, 12 patients in the IST group responded, while 5 patients did not achieve remission and 2 patients had disease relapse. At both 3 and 6 months after treatment, the proportion of transfusion-independent patients was higher in the UCBT group than in the IST group. Faster immune recovery and earlier transfusion independence further reduced the risk of infection and bleeding, thereby improving health-related quality of life in the UCBT-treated group. Our results suggested that UCBT as upfront therapy may be an effective and safe option for pediatric SAA patients, with favorable outcomes in experienced centers.

Fanconi Anemia Complementary Group A (FANCA) Facilitates the Occurrence and Progression of Liver Hepatocellular Carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a serious liver disease worldwide, and its pathogenesis is complicated. AIMS: This study investigated the potential role of FANCA in the advancement and prognosis of LIHC. METHODS: Public databases, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunohistochemistry (IHC) were employed to measure FANCA expression between tumor and normal samples. The relationship between FANCA expression and prognosis of LIHC patients were examined. Functional enrichment of FANCA-related genes was performed. Furthermore, univariate and multivariate analyses were conducted to determine the independent prognosis value of FANCA in LIHC. Finally, influence of FANCA knockout on the proliferation, migration, and invasion of HepG2 cell was validated with cloning formation, CCK8, and Transwell assays. RESULTS: Expression analysis presented that FANCA had high expression level in LIHC tissues and cells. Receiver operating characteristic (ROC) curve analysis showed that FANCA was of great diagnosis value in LIHC. Clinicopathological analysis revealed that FANCA was significantly greater expressed in the advanced stage than in the early stage of LIHC. Univariate, multivariate, and Kaplan-Meier survival analysis confirmed that high expression of FANCA was strongly associated with poor survival of LIHC patients. In addition, high level of FANCA in LIHC showed a negative association with immunoinfiltrated B cells, T cells, and stromal scores. Moreover, Knockout of FANCA significantly inhibited HepG2 cell proliferative activity, migration, and invasion ability. CONCLUSIONS: Our data revealed that high level of FANCA was closely associated with LIHC malignant progression, suggesting its potential utility as a diagnostic, predictive indicator, and therapeutic target.

A fungal CFEM-containing effector targets NPR1 regulator NIMIN2 to suppress plant immunity.

Colletotrichum fructicola causes a broad range of plant diseases worldwide and secretes many candidate proteinous effectors during infection, but it remains largely unknown regarding their effects in conquering plant immunity. Here, we characterized a novel effector CfEC12 that is required for the virulence of C. fructicola. CfEC12 contains a CFEM domain and is highly expressed during the early stage of host infection. Overexpression of CfEC12 suppressed BAX-triggered cell death, callose deposition and ROS burst in Nicotiana benthamiana. CfEC12 interacted with apple MdNIMIN2, a NIM1-interacting (NIMIN) protein that putatively modulates NPR1 activity in response to SA signal. Transient expression and transgenic analyses showed that MdNIMIN2 was required for apple resistance to C. fructicola infection and rescued the defence reduction in NbNIMIN2-silenced N. benthamiana, supporting a positive role in plant immunity. CfEC12 and MdNPR1 interacted with a common region of MdNIMIN2, indicating that CfEC12 suppresses the interaction between MdNIMIN2 and MdNPR1 by competitive target binding. In sum, we identified a fungal effector that targets the plant salicylic acid defence pathway to promote fungal infection.

Focusing on the Abnormal Events of NPC1, NPC2, and NPC1L1 in Pan-Cancer and Further Constructing LUAD and KICH Prediction Models.

Cancer's high incidence and death rate jeopardize human health and life, and it has become a global public health issue. Some members of NPCs have been studied in a few cancers, but comprehensive and prognostic analysis is lacking in most cancers. In this study, we used the Cancer Genome Atlas (TCGA) data genomics and transcriptome technology to examine the differential expression and prognosis of NPCs in 33 cancer samples, as well as to investigate NPCs mutations and their effect on patient prognosis and to evaluate the methylation level of NPCs in cancer. The linked mechanisms and medication resistance were subsequently investigated in order to investigate prospective tumor therapy approaches. The relationships between NPCs and immune infiltration, immune cells, immunological regulatory substances, and immune pathways were also investigated. Finally, the LUAD and KICH prognostic prediction models were built using univariate and multivariate COX regression analysis. Additionally, the mRNA and protein levels of NPCs were also identified.

A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization-fresh embryo transferred in infertile women.

In areas with high incidence of tuberculosis (TB), there are more infertile women who underwent in vitro fertilization (IVF) and have latent TB infection (LTBI), and thus, their potential risks should be paid enough attention. The purpose of our study aimed to analyze the relationship between LTBI and clinical pregnancy outcomes of IVF and fresh embryo transfer (IVF-FET). This was a retrospective study of 628 infertile women who had undergone IVF-FET in the Fourth Affiliated Hospital of Hebei Medical University from January 2019 to December 2021. The women experienced no clinical symptoms, negative imaging, and T-SPOT.TB-positive diagnosis of LTBI. We divided the study population into the LTBI group and the non-LTBI group. The clinical pregnancy rate in the LTBI group was significantly lower than that in the non-LTBI group (40.54% vs 49.51%, P = 0.031), and there was no significant difference in live birth rate and miscarriage rate between the two groups. Logistic regression analysis showed that LTBI was an independent risk factor for decreased clinical pregnancy rate in infertile women undergoing IVF-FET. In conclusion, LTBI affects clinical pregnancy rate of IVF-FET in infertile women, and therefore, clinicians (especially in countries with a high TB burden) need to pay attention to LTBI before IVF and embryo transfer.

Machine learning algorithms for a novel cuproptosis-related gene signature of diagnostic and immune infiltration in endometriosis.

Endometriosis (EMT) is an aggressive disease of the reproductive system, also called "benign cancer". However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.

MicroRNA-367-3p directly targets RAB23 and inhibits proliferation, migration and invasion of bladder cancer cells and increases cisplatin sensitivity.

OBJECTIVES: This study investigated the biological role of miR-367-3p upregulation in bladder cancer and verified the mutual relation between miR-367-3p and RAB23. MATERIALS AND METHODS: Expression levels of miR-367-3p were determined by RT-qPCR in bladder cancer cell lines and human bladder cancer tissues. The effects of miR-367-3p on proliferation, migration and invasion were evaluated by cell colony formation assays, wound healing assays and trans-well assays, respectively. The effects of miR-367-3p and RAB23 on cisplatin sensitivity of bladder cancer cells were assessed by CCK-8 assay. The expression of its target-RAB23 was determined by western blotting in T24, 5637. Plasmids used in dual-luciferase assays were constructed to confirm the action of miR-367-3p on downstream target-RAB23 in T24 cells. And also, the role of miR-367-3p in tumorigenesis was also confirmed in nude mouse models. RESULTS: The downregulation of miR-367-3p was observed in human bladder cancer tissues. MiR-367-3p downregulation positively correlated with tumor stage and tumor grade. MiR-367-3p overexpression in T24, 5637 cells suppressed the proliferation, migration, and invasion of bladder cancer cells in vitro while decreasing IC50 values under T24 and 5637 cisplatin treatment conditions. RAB23 was shown to be upregulated in bladder cancer tissues and cell lines. MiR-367-3p directly bound to the 3' UTR of RAB23 in T24 cells. RAB23 was potentially accounted for the aforementioned functions of miR-367-3p. Tumor formation experiments in nude mouse models confirmed that overexpression of miR-367-3p could inhibit tumor growth and invasion in vivo. CONCLUSIONS: miR-367-3p acts as a tumor suppressor in bladder cancer by downregulating RAB23 signaling. We conjecture that miR-367-3p-mediated downregulation of RAB23 expression may be a new therapeutic strategy for bladder cancer treatment.

A predictive model combining clinical characteristics and nutritional risk factors for overall survival after umbilical cord blood transplantation.

BACKGROUND: Umbilical cord blood transplantation (UCBT) is a curable therapy for hematological disease; however, the impact of nutritional status on UCBT outcomes remains controversial. To evaluate the joint effect of clinical characteristics and nutritional status on the prognosis of patients who underwent UCBT, we screened various factors to establish a predictive model of overall survival (OS) after UCBT. METHODS: We performed an integrated clinical characteristic and nutritional risk factor analysis and established a predictive model that could be used to identify UCBT recipients with poor OS. Internal validation was performed by using the bootstrap method with 500 repetitions. RESULTS: Four factors, including disease status, conditioning regimen, calf skinfold thickness and albumin level, were identified and used to develop a risk score for OS, which showed a positive predictive value of 84.0%. A high-risk score (≥ 2.225) was associated with inferior 3-year OS post-UCBT [67.5% (95% CI 51.1-79.4%), P = 0.001]. Then, we built a nomogram based on the four factors that showed good discrimination with a C-index of 0.833 (95% CI 0.743-0.922). The optimism-corrected C-index value of the bootstrapping was 0.804. Multivariate analysis suggested that a high calf skinfold thickness (≥ 20.5 mm) and a low albumin level (< 33.6 g/L) conferred poor disease-free survival (DFS). CONCLUSION: The predictive model combining clinical and nutritional factors could be used to predict OS in UCBT recipients, thereby promoting preemptive treatment.

Potassium alleviates over-reduction of the photosynthetic electron transport chain and helps to maintain photosynthetic function under salt-stress.

Potassium ions enhance photosynthetic tolerance to salt stress. We hypothesized that potassium ions, by minimizing the trans-thylakoid proton diffusion potential difference, can alleviate over-reduction of the photosynthetic electron transport chain and maintain the functionality of the photosynthetic apparatus. This study investigated the effects of exogenous potassium on the transcription level and activity of proteins related to the photosynthetic electron-transport chain of tobacco seedlings under salt stress. Salt stress retarded the growth of seedlings and caused an outflow of potassium ions from the chloroplast. It also lowered qP (indicator of the oxidation state of QA , the primary quinone electron acceptor in Photosystem II (PSII) and YPSII (average photochemical yield of PSII in the light-adapted state) while increasing YNO+NF (nonregulatory energy dissipation in functional and nonfunctional PSII), accompanied by decreased expression of most light-harvesting, energy-transduction, and electron-transport genes. However, exogenous potassium prevented these effects due to NaCl. Interestingly, lincomycin (an inhibitor of the synthesis of chloroplast-encoded proteins in PSII) significantly diminished the alleviation effect of exogenous potassium on salt stress. We attribute the comprehensive NaCl-induced downregulation of transcription and photosynthetic activities to retrograde signaling induced by reactive oxygen species. There probably exist at least two types of retrograde signaling induced by reactive oxygen species, distinguished by their sensitivity to lincomycin. Exogenous potassium appears to exert its primary effect by ameliorating the trans-thylakoid proton diffusion potential difference via a potassium channel, thereby accelerating ATP synthesis and carbon assimilation, alleviating over-reduction of the photosynthetic electron transport chain, and maintaining the functionality of photosynthetic proteins.