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Li-Yi Wang,1 Mei-Zhi Li,2 Xiao-Jian Jiang,1 Yang Han,3 Juan Liu,4 Ting-Ting Xiang,1 Zheng-Min Zhu1 1College of Nursing, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Nursing, Hunan Provincial Brain Hospital, Changsha, Hunan, People’s Republic of China; 3College of Civil Engineering, Central South University, Changsha, Hunan, People’s Republic of China; 4College of Basic Medicine, Ningxia Medical University, Yinchuang, Ningxia, People’s Republic of ChinaCorrespondence: Xiao-Jian Jiang, College of Nursing, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Tel +86 14781276032, Email yzjxj726@163.com Yang Han, College of Civil Engineering, Central South University, Changsha, Hunan, 410075, People’s Republic of China, Tel +86 15111314076, Email 214801060@csu.edu.cnPurpose: To explore the mediating effect of self-efficacy on the relationship between perceived social support and resilience in patients with recurrent schizophrenia in China.Patients and Methods: In this cross-sectional study, a total of 176 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, completed a general data questionnaire, the Connor Davidson Resilience Scale (CD-RISC), the Perceived Social Support Scale (PSSS) and the General Self-Efficacy Energy Scale (GSES).Results: Among the 176 patients, the mean GSES score was 2.02± 0.61, the mean PSSS score was 56.77± 14.61, and the mean CD-RISC score was 58.06± 17.26. Self-efficacy played a partial mediating role between social support and resilience, and the mediating effect accounted for 42.56% of the total effect.Conclusion: The resilience level of patients with recurrent schizophrenia in China is moderate and needs to be improved. This research revealed that self-efficacy played a part in mediating perceived social support and resilience in patients with recurrent schizophrenia in China. Perceived social support can indirectly affect resilience in patients with recurrent schizophrenia through self-efficacy. Comprehensive interventions in perceived social support and self-efficacy would help to improve the resilience of patients with recurrent schizophrenia.Keywords: recurrent schizophrenia, perceived social support, self-efficacy, resilience, mediating effect

Ligand-protected metal nanoclusters provide an ideal platform for investigating photoredox catalysis. The central challenge is balancing their stability and catalytic activity. Here we show a photochemical reduction-oxidation cascade method for synthesizing an Au 8 Cu 6 nanocluster, which features a robust structure and active surface. Photoredox catalytic activity of Au 8 Cu 6 is developed for the functionalization of alkynes under oxidative conditions. Mechanism studies based on the precise structure reveal the catalytic process of the Au 8 Cu 6 nanocluster. Oxidant-dependent selectivity of Au 8 Cu 6 catalysis is developed for chemodivergent synthesis of mono- and di-functionalized products in high efficiency. The results will stimulate more research on metal nanocluster synthesis and catalysis., (© 2024. The Author(s).)

Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Although the Japanese encephalitis virus (JEV) infects various cell types, its receptor molecules are still not clearly understood. In our laboratory's prior research, Rab4b was identified as a potential host factor that facilitates JEV infection in PK15 cells, utilizing a genome-wide CRISPR/Cas9 knockout library (PK-15-GeCKO). To further explore the effect of Rab4b on JEV replication, we used the Rab4b knockout PK15 cell line using the CRISPR/Cas9 technology and overexpressing the Rab4b PK15 cell line, with IFA, RT-qPCR, and Western blot to study the effect of Rab4b on viral replication in the whole life cycle of the JEV. The results show that the knockout of Rab4b inhibited the replication of the JEV in PK15 cells, and the overexpression of Rab4b promoted the replication of the JEV in PK15 cell lines. Furthermore, we demonstrated for the first time that host factor Rab4b facilitates the adsorption, internalization, assembly, and release of the JEV, thereby promoting JEV replication. This study enriches the regulatory network between the JEV and host factors and lays the experimental foundation for further understanding of the function of the Rab4b protein.

Background: Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain., Aim: To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians., Methods: A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors., Results: The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS., Conclusion: Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered., Competing Interests: Conflict-of-interest statement: All the authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the value of serum free light chain (sFLC) and serum calcium ion in the diagnosis and prognosis of multiple myeloma (MM)., Methods: Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group, and 40 healthy volunteers were selected as the control group. The differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc between the two groups were compared. Meanwhile, the differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc in different international staging systems (ISS), chemotherapy efficacy and prognosis patients were analyzed., Results: The levels of sFLC-κ［(98.39±21.19) vs (12.01±4.45) mg/L］, sFLC-λ［(210.20±45.54) vs (14.10±5.11) mg/L］ and proportions of hypocalcemia （65% vs 0） in the observation group were significantly higher than those in the control group ( P < 0.05), while sFLC-κ/ λ ratio［（0.44±0.10） vs (0.87±0.12)］ and serum calcium ions ［（1.98±0.46） vs （2.42±0.40）mmol/L］ were significantly lower than those in the control group ( P < 0.05). The sFLC-κ, sFLC-λ, the proportion of hypocalcemia and the course of hypocalcemia in ISS stage III patients in the observation group were significantly higher than those in stage I and II patients ( P < 0.05), while sFLC-κ/λ ratio, and serum calcium ions were significantly lower than those in stage I and II patients ( P < 0.05). The levels of sFLC-κ ［（107.76±21.22） vs （94.67±20.11）mg/L］, sFLC- λ［（245.54±41.12） vs （205.54±50.22）mg/L］ of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia ( P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia ［（0.42±0.04） vs （0.47±0.06）； P < 0.05］. The levels of sFLC-κ ［(107.29±20.14） vs （ 91.11±18.92）mg/L］, sFLC-λ［（247.98±42.26） vs （179.29±39.32）mg/L］ in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy ( P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy ［(0.43±0.10) vs (0.50±0.09)； P < 0.05）］. The area under the ROC curve for sFLC-κ, sFLC-λ, sFLC-κ/λ predicting ineffective chemotherapy was 0.803, 0.793 and 0.699 respectively, P < 0.05. There was no significant difference in sFLC-κ, sFLC-λ, sFLC-κ/λ ratio, serum calcium ion, hypocalcemia ratio and hypocalcemia course between survival and death patients ( P >0.05)., Conclusion: sFLC and serum calcium are related to ISS stage of MM patients. sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients. However, the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

In this study, we analyzed and verified differentially expressed genes (DEGs) in ROS and KEAP1 crosstalk in oncogenic signatures using GEO data sets (GSE4107 and GSE41328). Multiple pathway enrichment analyses were finished based on DEGs. The genetic signature for colorectal adenocarcinoma (COAD) was identified by using the Cox regression analysis. Kaplan-Meier survival and receiver operating characteristic curve analysis were used to explore the prognosis value of specific genes in COAD. The potential immune signatures and drug sensitivity prediction were also analyzed. Promising small-molecule agents were identified and predicted targets of α-hederin in SuperPred were validated by molecular docking. Also, expression levels of genes and Western blot analysis were conducted. In total, 48 genes were identified as DEGs, and the hub genes such as COL1A1, CXCL12, COL1A2, FN1, CAV1, TIMP3, and IGFBP7 were identified. The ROS and KEAP1-associated gene signatures comprised of hub key genes were developed for predicting the prognosis and evaluating the immune cell responses and immune infiltration in COAD. α-hederin, a potential anti-colorectal cancer (CRC) agent, was found to enhance the sensitivity of HCT116 cells, regulate CAV1 and COL1A1, and decrease KEAP1, Nrf2, and HO-1 expression significantly. KEAP1-related genes could be an essential mediator of ROS in CRC, and KEAP1-associated genes were effective in predicting prognosis and evaluating individualized CRC treatment. Therefore, α-hederin may be an effective chemosensitizer for CRC treatments in clinical settings., (© 2024 Wiley Periodicals LLC.)

HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To define the predictive factors of severe retinopathy of prematurity (ROP) and develop a nomogram for predicting severe ROP in southeast China., Methods: Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children's Hospital were included. Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively. Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction, which was compared with WINROP model and Digirop-Birth model., Results: Infants from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University ( n =478) were randomly allocated into training ( n =402) and internal validation group ( n =76). Infants from Taizhou Women and Children's Hospital were set as external validation group ( n =76). Severe ROP were found in 52 of 402 infants, 12 of 76 infants, and 7 of 76 infants in training group, internal validation group, and external validation group, respectively. Birth weight [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.996-0.999; P <0.001], multiple births (OR, 1.885; 95%CI, 1.013-3.506; P =0.045), and non-invasive ventilation (OR, 0.288; 95%CI, 0.146-0.570; P <0.001) were identified as predictive factors for the prediction of severe ROP, by univariate analysis and multivariate analysis. For predicting severe ROP based on the internal validation group, the areas under receiver operating characteristic curve (AUC) was 78.1 (95%CI, 64.2-92.0) for the nomogram, 32.9 (95%CI, 15.3-50.5) for WINROP model, 70.2 (95%CI, 55.8-84.6) for Digirop-Birth model. In external validation group, AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model (80.2 versus 51.1 and 63.4). The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model. The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability., Conclusion: Birth weight, multiple births, and non-invasive ventilation are independent predictors of severe ROP. The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China., Competing Interests: Conflicts of Interest: Liu D, None; Li XY, None; He HW, None; Jin KL, None; Zhang LX, None; Zhou Y, None; Zhu ZM, None; Jiang CC, None; Wu HJ, None; Zheng SL, None., (International Journal of Ophthalmology Press.)

Objective: To investigate the clinical and prognostic characteristics of newly diagnosed multiple myeloma (NDMM) patients with myelofibrosis (MF). Methods: The clinical data of 160 NDMM patients admitted to Henan Provincial People's Hospital from January 2012 to July 2022 were analyzed retrospectively. They were divided into MF group( n =74) and non-MF group( n =86) according to whether combined with MF. Patients in MF group were further splited into MF-1 group ( n =47) and MF-2/3 group ( n =27). All patients were treated with bortezomib and immunomodulatory-based combination therapy. The efficacy was evaluated after 4 courses, and the clinical features and prognosis between the two groups were compared. The deadline for follow-up was December 30, 2022 and the median follow-up period [ M ( Q 1 , Q 3 )] was 23.5 (14.4, 40.5) months. Kaplan-Meier method was used for survival analysis, and Cox regression model was used to analyze the influencing factors of survival. Results: Among 160 patients with NDMM, 91 were males and 69 were females, with a median age [ M ( Q 1 , Q 3 )] of 59 (54, 69) years. In MF group, the bone marrow immature plasma cell percentage, total plasma cell percentage were 9.6% (3.2%, 28.5%) and 36.4% (18.5%, 51.1%), respectively, which were higher than 6.0% (1.2%, 17.2%) and 24.0% (12.0%, 46.0%) of the non-MF group (both P <0.05). Hb level was 84.0(74.5, 100.5)g/L and PLT was (151.99±90.68) ×10 9 /L in the MF group, which were lower than 96.0 (81.0, 112.0)g/L and (180.38±85.32) ×10 9 /L of non-MF group (both P <0.05). But there were no significant differences in ISS stage, karyotypic and fluorescence in situ hybridization (FISH) high-risk genetic abnormalities between the two groups (all P >0.05). Objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) were not significantly different between the two groups (all P >0.05). The rate of 17p- was 25.9% (7/27) in MF-2/3 group, which was higher than 8.1% (7/86) of non-MF group ( P =0.049). The median OS of the MF-2/3 group was 25.0 ( 95%CI : 23.6-26.4) months, which was shorter than that of the non-MF group (54.0 months, P =0.031). Multivariate Cox regression analysis showed that grade MF-2/3 was not a risk factor for OS in NDMM patients ( HR =1.507, 95%CI : 0.624-3.993, P =0.425). Conclusions: The ratio of bone marrow immature plasma cells and total plasma cells in NDMM patients with MF are higher than that in patients without MF, and the Hb and PLT are lower than that in patients without MF. NDMM patients with grade 2/3 MF have shorter survival than those without MF.

Four group 10 metal nanoclusters, Ni 10 (4-MePhS) 20 , Ni 11 (PhS) 22 , Pd 9 (PhS) 18 and Pd 10 (PhS) 20 were synthesized from disulfides based on a photochemical reduction-oxidation cascade process, which proceeds via a different mechanism to that of the conventional two-step reduction process. The as-obtained nanoclusters possess oxidative resistance and structural robustness under different conditions. Their atomically precise structures are determined to be nickel or palladium rings in which the metal atoms are bridged by Ar-S groups. Their catalytic performance in oxygen reduction reaction was compared, and the ring size-dependent catalytic activity of the group 10 metal nanoclusters was revealed. This work provides an efficient route to atomically precise and structurally stable group 10 metal nanoclusters, and sheds light on their further applications in electrocatalysis.

Objective: Lung cancer (LC) is the highest contributor to cancer-associated mortality worldwide. Approximately 85% of all LC incidences involve non-small cell LC (NSCLC). Unfortunately, owing to a significant lack of sensitive and robust bioindicators, most patient diagnoses occur at advanced stages of the disease, thereby resulting in extremely poor patient outcomes. Herein, we elucidated the role of interleukin-17A (IL-17A) among NSCLC patients., Materials and Methods: Circulating IL-17A content was measured using enzyme-linked immunosorbent assay (ELISA), and its diagnostic and prognostic abilities were assessed using the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, respectively., Results: Our analysis revealed that circulating IL-17A levels were significantly augmented among NSCLC vs. control samples. Moreover, based on our area under the curve (AUC) analysis, circulating IL-17A levels fared considerably better than the standard bioindicator carcinoembryonic antigen (CEA) in both testing and validation cohorts. Notably, we also revealed that the circulating IL-17A levels were accurately and reliably predicted in early-stage NSCLC patients. Besides, we demonstrated a strong correlation between elevated circulating IL-17A expression and worse prognosis among NSCLC patients., Conclusions: Herein, we demonstrated that circulating IL-17A levels can serve as reliable and potent diagnostic and prognostic bioindicators for NSCLC.

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg ( P= 0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol ( P= 0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg ( P= 0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg ( P= 0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg ( P= 0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P= 0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant ( P =0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P =0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

Purpose: The aim of this study is to evaluate the anatomical factors influencing elasticity values of normal testicular parenchyma using shear wave elastography (SWE)., Methods: This study examined 68 healthy male volunteers (117 testes in which standard transverse axis ultrasonography views could be obtained) via conventional scrotal ultrasonography and SWE. Both the mean (E Mean ) and standard deviation (E SD ) elasticity values were acquired., Results: In the standard transverse axis view of the rete testis at the mid-lateral edge of the testes, the E Mean values in 2mm the testicular parenchyma from the rete testis and the testicular capsule at the same level as the rete testis were all significantly larger than in the central zone (P<0.001, P<0.001, respectively). The E Mean value in the testicular parenchyma 2mm from the testicular capsule on the line formed approximately 45° below the horizontal line of the rete testis was significantly larger than in the rete testis approximately 45° above the horizontal line (P<0.001). In two standard transverse axis views, the E SD values in other regions were significantly larger than those in the central zones (all P<0.001). Also, the E Mean values in the transmediastinal arteries were larger than those of the surrounding normal testicular parenchyma (P<0.001)., Conclusion: Based on SWE, factors including the testicular capsule, the density of testicular fibrous septa, the depth of the Q-Box™, and the transmediastinal artery may influence the testes elasticity measurement., (Copyright © 2023 Asociación Española de Andrología, Medicina Sexual y Reproductiva. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A-binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes. Main body Pre-mRNA alternative splicing, a process that generates multiple splice isoforms from multi-exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre-mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA-binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression. Conclusion This review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A-dependent alternative splicing in tumour therapies., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Due to poor T cell infiltration, tumors evade immune surveillance. Increased CD8 + T cell infiltration in breast cancer suggests a satisfactory response to immunotherapy. COPS6 has been identified as an oncogene, but its role in regulating antitumor immune responses has not been defined. In this study, we investigated the impact of COPS6 on tumor immune evasion in vivo. Tumor transplantation models were established in C57BL/6 J mice and BALB/c nude mice. Flow cytometry was conducted to identify the role of COPS6 on tumor-infiltrating CD8 + T cells. By analyzing the TCGA and GTEx cohort, we found that COPS6 expression was significantly up-regulated in a variety of cancers. In human osteosarcoma cell line U2OS and non-small cell lung cancer cell line H1299, we showed that p53 negatively regulated COPS6 promoter activity. In human breast cancer MCF-7 cells, COPS6 overexpression stimulated p-AKT expression as well as the proliferation and malignant transformation of tumor cells, whereas knockdown of COPS6 caused opposite effects. Knockdown of COPS6 also significantly suppressed the growth of mouse mammary cancer EMT6 xenografts in BALB/c nude mice. Bioinformatics analysis suggested that COPS6 was a mediator of IL-6 production in the tumor microenvironment and a negative regulator of CD8 + T cell tumor infiltration in breast cancer. In C57BL6 mice bearing EMT6 xenografts, COPS6 knockdown in the EMT6 cells increased the number of tumor-infiltrating CD8 + T cells, while knockdown of IL-6 in COPS6KD EMT6 cells diminished tumor infiltrating CD8 + T cells. We conclude that COPS6 promotes breast cancer progression by reducing CD8 + T cell infiltration and function via the regulation of IL-6 secretion. This study clarifies the role of p53/COPS6/IL-6/CD8 + tumor infiltrating lymphocytes signaling in breast cancer progression and immune evasion, opening a new path for development of COPS6-targeting therapies to enhance tumor immunogenicity and treat immunologically "cold" breast cancer., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT., (© 2023 Wiley Periodicals LLC.)

Human papillomavirus (HPV) infection is a causative agent of cervical cancer (CC). N6-methyladenosine (m6A) modification is implicated in carcinogenesis and tumor progression. However, the involvement of m6A modification in HPV-involved CC remains unclear. Here we showed that HPV E6/7 oncoproteins affected the global m6A modification and E7 specifically promoted the expression of ALKBH5. We found that ALKBH5 was significantly upregulated in CC and might serve as a valuable prognostic marker. Forced expression of ALKBH5 enhanced the malignant phenotypes of CC cells. Mechanistically, we discovered that E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27Ac and H3K4Me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Moreover, ALKBH5 promoted tumorigenesis and metastasis of CC by regulating PAK5. Overall, our findings herein demonstrate a significant role of ALKBH5 in CC progression in HPV-positive cells. Thus, we propose that ALKBH5 may serve as a prognostic biomarker and therapeutic target for CC patients., Competing Interests: Declaration of Competing Interest All listed authors of this manuscript have approved of the manuscript to submit to Pharmacological Research including its copyright transfer at acceptance for publication. The authors declare that there is no conflict of interest associated with this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Practical approaches to the synthesis of atomically precise metal nanoclusters are in high demand as they provide the structural basis for investigating nanomaterials' structure-property correlations with atomic precision. The Brust-Schiffrin method has been widely used, while the essential reductive ligands (e.g., thiols) limit the application of this method for synthesizing metal nanoclusters with specific frameworks and surface ligands. In this work, we developed a photochemical route for synthesizing atomically precise metal nanoclusters by applying disulfide, which is a widely available, stable, and environmentally friendly sulfur source. This method enables the construction of structurally diverse metal nanoclusters and especially features the synthesis of PhS-protected metal nanoclusters that were not easily achieved previously and the gram-scale synthesis. A reduction-oxidation cascade mechanism has been revealed for the photochemical route. This work is expected to open up new opportunities for metal nanocluster synthesis and will contribute to the practical applications of this kind of nanomaterial.

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Atomically precise metal nanoclusters have received tremendous attention due to their unique structures and properties. Although synthetic approaches to this kind of nanomaterial have been well developed, methods toward precision functionalization of the as-synthesized metal nanoclusters are extremely limited, hindering their interfacial modification and related performance improvement. Herein, an amidation strategy has been developed for the precision functionalization of the Au 11 nanocluster based on preorganized nitrogen sites. The nanocluster amidation did not change the number of gold atoms in the Au 11 kernel and their bonding mode to the surface ligands but slightly modified the arrangement of gold atoms with the introduction of functionality and chirality, thus representing a relatively mild method for the modification of metal nanoclusters. The stability and oxidation barrier of the Au 11 nanocluster are also improved accordingly. The method developed here would be a generalizable strategy for the precision functionalization of metal nanoclusters.

Introduction: Indigofera L. is the third largest genus in Fabaceae and includes economically important species that are used for indigo dye-producing, medicinal, ornamental, and soil and water conservation. The genus is taxonomically difficult due to the high level of overlap in morphological characters of interspecies, fewer reliability states for classification, and extensive adaptive evolution. Previous characteristic-based taxonomy and nuclear ITS-based phylogenies have contributed to our understanding of Indigofera taxonomy and evolution. However, the lack of chloroplast genomic resources limits our comprehensive understanding of the phylogenetic relationships and evolutionary processes of Indigofera ., Methods: Here, we newly assembled 18 chloroplast genomes of Indigofera . We performed a series of analyses of genome structure, nucleotide diversity, phylogenetic analysis, species pairwise Ka/Ks ratios, and positive selection analysis by combining with allied species in Papilionoideae., Results and Discussion: The chloroplast genomes of Indigofera exhibited highly conserved structures and ranged in size from 157,918 to 160,040 bp, containing 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Thirteen highly variable regions were identified, of which trn K- rbc L, ndh F- trn L, and ycf 1 were considered as candidate DNA barcodes for species identification of Indigofera . Phylogenetic analysis using maximum likelihood (ML) and Bayesian inference (BI) methods based on complete chloroplast genome and protein-coding genes (PCGs) generated a well-resolved phylogeny of Indigofera and allied species. Indigofera monophyly was strongly supported, and four monophyletic lineages (i.e., the Pantropical, East Asian, Tethyan, and Palaeotropical clades) were resolved within the genus. The species pairwise Ka/Ks ratios showed values lower than 1, and 13 genes with significant posterior probabilities for codon sites were identified in the positive selection analysis using the branch-site model, eight of which were associated with photosynthesis. Positive selection of accD suggested that Indigofera species have experienced adaptive evolution to selection pressures imposed by their herbivores and pathogens. Our study provided insight into the structural variation of chloroplast genomes, phylogenetic relationships, and adaptive evolution in Indigofera . These results will facilitate future studies on species identification, interspecific and intraspecific delimitation, adaptive evolution, and the phylogenetic relationships of the genus Indigofera ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Wang, Yan, Zhu, Gao and Zhao.)

HLA-A*02:07:22 differs from HLA-A*02:07:01:01 by one nucleotide in exon 3., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, -1.3 mm Hg [-5.8, 3.2]; diastolic pressure, -.3 mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, -3.6 mm Hg [-5.9, -1.3]; diastolic pressure, -2.1 mm Hg [-3.5, -.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Purpose: There are limited studies on the use of bronchodilators for the treatment of bronchiectasis. This study investigated the efficacy of tiotropium in patients with bronchiectasis and airflow limitation., Methods: This study was a prospective cohort study, including 169 patients with bronchiectasis and airflow limitation from 2015 to 2019. The clinical outcomes observed in our study were the effect of tiotropium on the frequency of moderate exacerbations, the time to the first severe exacerbation, and the annual decline in FEV 1 ., Results: After 12 months, the annual decline in the FEV 1 after bronchodilator use was 27.08 ml or 42.9 ml per year in the group with or without tiotropium, respectively. Treatment with tiotropium was associated with a decreased risk of moderate exacerbation of bronchiectasis (Adjusted RR 0.618 95% CI 0.493-0.774; P < 0.005). The time to the first severe acute exacerbation of bronchiectasis in the tiotropium group was longer than the non-tiotropium group (Adjusted HR 0.333 95% CI 0.219-0.506; P < 0.001)., Conclusion: In conclusion, prospective cohort study showed that tiotropium effectively ameliorated the annual decline in the FEV 1, with a lower-risk rate of moderate exacerbations and prolonging the time to the first-time severe exacerbation in patients with bronchiectasis and airflow limitation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Capsaicin, a functional component of chili pepper, possesses anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to determine the property of capsaicin against hepatocarcinogenesis in vivo and investigate the role of the SIRT1/SOX2 pathway in the mode of action of capsaicin in hepatic progenitor cells (HPCs), which is related to hepatocarcinogenesis., Materials & Methods: We prepared a diethylnitrosamine-induced liver cancer model in rats to examine hepatocarcinogenesis, and delivered liposomal capsaicin through the subcutaneous transposition of the spleen to the liver. Liver sections from rats and hepatocarcinoma patients were stained for the markers of HPCs or SIRT1/SOX2 signaling. SIRT1/SOX2 signalling expression was measured using immunoprecipitation and western blot., Results: We found that capsaicin significantly inhibited hepatocarcinogenesis. Notably, capsaicin inhibited HPCs activation in vivo but did not induce apoptosis in the normal hepatic progenitor cell line in rats in vitro. This suggests that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs. Moreover, capsaicin can induce this inhibition by reducing the stability of SOX2. SIRT1 is overexpressed in liver cancer and acts as a tumor promoter via SOX2 deacetylation. Using immunoprecipitation, we identified direct binding between SIRT1 and SOX2. The capsaicin treatment resulted in SIRT1 downregulation which reduced deacetylation, and increased nuclear export as well as subsequent ubiquitous degradation of SOX2., Conclusions: Altogether, we report that capsaicin suppresses hepatocarcinogenesis by inhibiting the stemness of HPCs via SIRT1/SOX2 signaling. It may serve as a promising therapeutic candidate for liver cancer., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The incidence of aging-related cognitive decline is increasing with population aging. It is urgent to explore ways to ameliorate aging-related cognitive decline. Cognitive-exercise dual-task intervention has shown beneficial effects on improving cognition in aging cohorts, but the mechanisms of the effects remain unclear. In this study, 18-month-old Sprague Dawley rats served as a model of natural aging. First, the performance in the Morris water maze test and the change in synaptophysin content in the hippocampus were used to investigate the cognitive decline of 18-month-old rats. Then, a batch of 18-month-old rats was treated with cognitive, exercise, or cognitive-exercise dual-task intervention for 12 weeks. The novel object recognition test was used to assess cognitive ability. Enzyme-linked immunosorbent assay and Western blotting were used to detect the levels of oxidative stress molecules and synaptic plasticity-related proteins. We found that cognitive-exercise dual-task intervention improved the discrimination index of natural aging rats. After dual-task intervention, the expression levels of synaptophysin, brain-derived neurotrophic factor, superoxide dismutase, and glutathione peroxidase were increased, and the expression level of lipid peroxide malondialdehyde was decreased. Furthermore, the effect of dual-task intervention on synaptic plasticity-related proteins and oxidative stress indicators was greater than that of single cognitive or exercise intervention. In conclusion, cognitive-exercise dual-task intervention can significantly ameliorate aging-related cognitive decline, and the improvement might be related to the reduction of oxidative stress and the enhancement of synaptic plasticity. The effect of cognitive-exercise dual-task intervention may be better than that of single cognitive or exercise intervention., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To study the effect of cordycepin on the expression of connexin 43 (CX43) in the corpus cavernosum tissue of the ED rats with type II diabetic mellitus (DM)., Methods: Forty male SD rats were fed with high-fat diet and injected intraperitoneally with STZ solution to induce type II DM, and then divided into 4 groups of an equal number: DM model control, low-dose cordycepin (10.0 mg/kg/d), high-dose cordycepin (30.0 mg/kg/d) and sildenafil positive control (5.0 mg/kg/d). Another 10 male SD rats were taken as blank controls and fed with normal diet. After 6 weeks of intervention, the sexual behavior of the rats was observed, the ratio of intra-cavernous pressure to mean arterial pressure (ICP/MAP) measured, and the corpus cavernosal tissue harvested for observation of the morphology and determination of the expression level of CX43 in the corpus cavernosum by immunohistochemistry., Results: Compared with the DM model controls, the rats in the high-dose cordycepin group showed significantly improved latency and frequency of captures (P < 0.01), increased ICP/MAP ratio (P < 0.05), and improved morphology of the corpus cavernosal tissue. The expression of CX43 was found mainly in the smooth muscle cells of the penile corpus cavernosum, and dramatically higher in the high-dose cordycepin group than in the DM model controls (P < 0.01)., Conclusion: Cordycepin can effectively improve the erectile function of type Ⅱ diabetic rats by up-regulating the expression of CX43 in the penile corpus cavernosum.

Objective: To evaluate the bladder function and sleep pattern in the children with primary mono-symptomatic nocturnal enuresis (PMNE) by the polysomnography (PSG) and ambulatory urodynamic monitoring (AUM). Methods: From October 2019 to October 2021, forty-three patients with PMNE were selected as PMNE group from the First Affiliated Hospital of Zhengzhou University and further subdivided into the severe PMNE group (enuresis>4 times/week) and the non-severe PMNE group (enuresis times 4 times/week) according to the severity. The conventional urodynamics (CUD), AUM, and PSG examinations and bladder diary were completed in the PMNE group. The control group consisted of 23 children with normal PSG findings and without the lower urinary tract symptoms. Results: The severe PMNE group included 9 males and 14 females, aged(12.1±3.2)years, and nocturnal enuresis number per week is 6.7±1.7. The non-severe PMNE group included 9 males and 11 females, aged(12.0±3.4)years, and nocturnal enuresis number per week is 2.3±1.0. The incidences of nocturnal polyuria and the reduction in maximum bladder capacity in the PMNE group was 34.9% and 11.6%, respectively. The incidence and frequency of detrusor overactivity (DO) in the severe PMNE group were significantly higher than those in the non-severe PMNE group [78.3% vs 45.0%, (5.5±1.8) times/h vs (3.4±1.0) times/h, respectively, all P <0.05]. It was found by the PSG that the severe PMNE group had significantly higher cortical arousal index, apnea hypopnea index (AHI), and percentage of N1+N2 phase in total sleep time, compared with the control group[(58.6±9.8)% vs (49.3±9.5)%, (9.4±4.4) times/h vs (3.1±1.5) times/h, (2.7±0.9) times/h vs (0.9±0.7) times/h] (all P <0.05). While the sleep efficiency of the severe PMNE group was substantially lower than that of the non-severe PMNE group [(86.4±4.3)% vs (91.0±3.9)%], the cortical arousal index and AHI were significantly greater than those of the non-severe PMNE group[(9.4±4.4) times/h vs (5.7±3.2) times/h, (2.7±0.9) times/h vs (1.9±0.7) times/h] (all P <0.05). In the PMNE group, there were positive correlations between cortical arousal index and nocturnal DO frequency or AHI ( r =0.705, 0.765, P =0.001). Conclusions: Children with PMNE have nocturnal bladder dysfunction and abnormal sleep pattern, and there is a certain correlation between them. PSG and AUM are necessary for the evaluation and treatment of children with PMNE.

Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zou, Zhu, Huang, Bu, Zhu and Yuan.)

Background: Orelabrutinib is a novel, small molecule, selective irreversible Bruton tyrosine kinase inhibitor. The purpose of this study was to evaluate the efficacy and safety of orelabrutinib in patients with relapsed or refractory Waldenström's macroglobulinemia (R/R WM)., Methods: This is a prospective, multicenter study of orelabrutinib in patients with WM who had at least one prior line of treatment. Orelabrutinib was administered orally at a daily dose of 150 mg until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR) assessed by the Independent Review Committee (IRC) according to IWWM-6. This study is registered with ClinicalTrials.gov, NCT04440059. This trial was also registered on Center for Drug Evaluation (www.chinadrugtrials.org.cn) in March 2019, with a number of CTR2019036., Findings: Between August 2019 and December 2020, 66 R/R WM patients were assessed for eligibility. Forty-seven eligible patients were evaluated for efficacy at a median follow-up of 16.4 months (interquartile range: 12.5, 19.5). As assessed by IRC, the MRR was 80.9%, and the overall response rate was 89.4%. The median time to at least a minor response was 1.9 months. The PFS rates was 89.4% at 12 months. For patients with MYD88 L265P / CXCR4 NEG , MYD88 L265P / CXCR4 S338X , and MYD88 NEG / CXCR4 NEG mutations, the MRRs were 84.6%, 100%, and 25.0%. Most adverse events were Grades 1 or 2 (91.0%). The common grade 3 or higher adverse events occurring were neutropenia (10.6%), thrombocytopenia (6.4%), and pneumonia (4.3%). Serious adverse events (SAE) occurred in 10 patients (21.3%). One treatment-related death was reported (hepatitis B reactivation)., Interpretation: Orelabrutinib has shown good efficacy and manageable safety profiles in patients with R/R WM., Funding: InnoCare Pharma., Competing Interests: DBZ, XXC, JJ, ZZF, SHY, WLZ, ZMS, WY, DJL, GHC, JDH, TL, YPS, BX, ZMZ, WX, and MZZ declare no competing interests. YMT, BZ, and RBZ are employees of InnoCare Pharma., (© 2022 The Author(s).)

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state. Methods: A total of 42 unaffected parents of ASD children (pASD) and 39 age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well. Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD ( ρ 1 = 0.298, P 1 = 0.007; ρ 2 = 0.220, P 2 = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ 3 = -0.334, P 3 = 0.002). Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Zhang, Zhu, Wang, Ding and Fang.)

Rosa glomerata is a diffuse shrub belonging to Rosa sect. Synstylae . It is endemic to Southwest China and of high ornamental and economic value. However, its systematic position remains unclear. Here, the complete chloroplast genome of R . glomerata was assembled using high-throughput sequencing data. The cp genome is 157,064 bp in length with a large single-copy region (LSC) of 86,216 bp, a small single-copy region (SSC) of 18,752 bp, and a pair of inverted repeats (IRs) of 26,048 bp. The overall GC content is 37.2%. A total of 137 genes were annotated, including 90 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis revealed that R . glomerata is closely related to R .  praelucens of R . sect. Microphyllae rather than species of R . sect. Synstylae ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To explore the characteristics, clinical features and prognostic effects of NOTCH1/FBXW7 gene mutations in T-cell acute lymphoblastic leukemia (T-ALL) patients. Methods: The clinical data of 61 T-ALL patients who underwent second-generation gene sequencing in Henan Provincial People's Hospital from March 2016 to March 2021 were retrospectively analyzed. There were 46 males and 15 females, with a median age [ M ( Q 1 , Q 3 )] of 18 (11, 30) years. The relationship between NOTCH1/FBXW7 gene mutation characteristics, clinical and laboratory parameters and their impact on event free survival (EFS) and overall survival (OS) were analyzed. Results: NOTCH1 gene mutations were found in 34 cases (55.7%, 34/61), including 22 cases of heterodimer domain (HD) mutations (64.7%), 7 cases of proline/glutamate/serine/threonine (PEST) mutations (20.6%), and 5 cases of both HD and PEST mutations (14.7%). FBXW7 gene mutations were detected in 9 cases (14.8%, 9/61), of which 5 cases had both NOTCH1 and FBXW7 gene mutations. Twenty-three (37.7%, 23/61) cases were wild type. The median white blood cell count of patients in NOTCH1/FBXW7 gene mutations group and wild-type group was 76.4×10 9 /L (8.3×10 9 /L, 149.2×10 9 /L), 54.1×10 9 /L (5.3×10 9 /L, 156.6×10 9 /L), respectively. Moreover, the hemoglobin was (89.1±27.1) g/L and (99.5±23.1) g/L, respectively, and the median proportion of bone marrow primordial cells was 84.5% (69.0%, 91.3%) and 60.0%(35.0%, 80.0%), respectively. The gene expression rate of SIL-TAL1, Hox11 and Hox11L2 was 7.9% (3/38) vs 17.4% (4/23), 18.4% (7/38) vs 4.3% (1/23), 5.3% (2/38) vs 13.0% (3/23), respectively (all P >0.05). However, the median platelet level in the NOTCH1/FBXW7 gene mutations group was 60.5×10 9 /L (36.8×10 9 /L, 100.3×10 9 /L), which was lower than that in the wild-type group [116.0×10 9 /L (63.0×10 9 /L, 178.0×10 9 /L)] ( P =0.018). The median number of gene mutations in the group with NOTCH1/FBXW7 gene mutations group was 2.5 (1.8, 4.0), which was more than that in the group without NOTCH1/FBXW7 gene mutations group [0 (0, 1.0)] ( P <0.001). The median EFS and OS of adult NOTCH1/FBXW7 gene mutations group were 28.0 (95% CI : 7.3-48.7) months and 30.0 (95% CI : 8.9-51.1) months, respectively, which were better than those of adult wild-type group [4.5 (95% CI : 0-11.6) months and 9.0 (95% CI : 0-19.1) months] ( P =0.008 and 0.014).The median EFS and OS of children NOTCH1/FBXW7 gene mutations group were 12.0 (95% CI : 10.4-13.6) months and 19.0 (95% CI : 13.6-24.4) months, respectively, and those of wild-type group were 10.0 (95% CI : 8.9-11.1) months and 21.0 (95% CI : 0-51.4) months, respectively ( P =0.673 and 0.434). Conclusions: The mutation rate of NOTCH1/FBXW7 gene is higher in T-ALL patients. Patients with NOTCH1/FBXW7 gene mutations group have lower platelet count and better EFS and OS. NOTCH1/FBXW7 gene mutation may be used as a hierarchical basis for individualized treatment of adult T-ALL patients.

The present paper aims to shed light on the influence of N6-methyladenosine (m6A) long non-coding RNAs (lncRNAs) and immune cell infiltration on colorectal cancer (CRC). We downloaded workflow-type data and xml-format clinical data on CRC from The Cancer Genome Atlas project. The relationship between lncRNA and m6A was identified by using Perl and R software. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed. Lasso regression was utilized to construct a prognostic model. Survival analysis was used to explore the relationship between clusters of m6A lncRNAs and clinical survival data. Differential analysis of the tumor microenvironment and an immune correlation analysis were used to determine immune cell infiltration levels in different clusters and their correlation with clinical prognosis. The expression of lncRNA was tightly associated with m6A. The univariate Cox regression analysis showed that lncRNA was a risk factor for the prognosis. Differential expression analysis demonstrated that m6A lncRNAs were partially highly expressed in tumor tissue. m6A lncRNA-related prognostic model could predict the prognosis of CRC independently. "ECM&#95;RECEPTOR&#95;INTERACTION" was the most significantly enriched gene set. PARP8 was overexpressed in tumor tissue and high-risk cluster. CD4 memory T cells, activated resting NK cells, and memory B cells were highly clustered in the high-risk cluster. All of the scores were higher in the low-risk group. m6A lncRNA is closely related to the occurrence and progression of CRC. The corresponding prognostic model can be utilized to evaluate the prognosis of CRC. m6A lncRNA and related immune cell infiltration in the tumor microenvironment can provide novel therapeutic targets for further research., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Serine hydroxymethyltransferase 2 (SHMT2) is the first rate-limiting enzyme for serine/glycine biosynthesis and one carbon metabolism. Here, we explore the underlying mechanism of how SHMT2 functions in renal cell carcinoma (RCC) initiation., Methods: In this study, SHMT2 expression was assessed in RCC tissues. In vitro experiments were performed to investigate the functional role of SHMT2. The detailed mechanisms of SHMT2-mediated PPAT were addressed., Results: Increased SHMT2 facilitated RCC cell proliferation by inducing the G1/S phase transition. And SHMT2 promoted the expression of PPAT. Mechanism dissection revealed that SHMT2 enhanced the m6A modification through the endogenous methyl donor SAM mediated by SHMT2 via serine/glycine one carbon metabolic networks. SHMT2-catalyzed serine/glycine conversion regulated PPAT expression in an m6A-IGF2BP2-dependent manner. SHMT2 promoted RCC cell proliferation by upregulating PPAT expression., Conclusions: SHMT2 promotes RCC tumorigenesis by increasing PPAT expression. Thus, SHMT2 may be a novel potential therapeutic target for RCC., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hemoglobin and albumin are associated with the prognosis of gastric cancer (GC) patients. However, the prognostic value of the hemoglobin to albumin ratio (HAR) for the short-term survival of GC patients with D2 radical resection has not been studied., Aim: To investigate the significance of the HAR in evaluating the short-term survival of GC patients after D2 radical resection and to construct a nomogram to predict the prognosis in GC patients after surgery, thus providing a reference for the development of postoperative individualized treatment and follow-up plans., Methods: Cox regression and Kaplan-Meier analysis was used for prognostic analysis. Logistic regression was used to analyze the relationships between HAR and the clinicopathological characteristics of the GC patients. A prognostic nomogram model for the short-term survival of GC patients was constructed by R software., Results: HAR was an independent risk factor for the short-term survival of GC patients. GC patients with a low HAR had a poor prognosis ( P < 0.001). Low HAR was markedly related to high stage [odds ratio (OR) = 0.45 for II vs I; OR = 0.48 for III vs I], T classification (OR = 0.52 for T4 vs T1) and large tumor size (OR = 0.51 for ≥ 4 cm vs < 4 cm) (all P < 0.05). The nomogram model was based on HAR, age, CA19-9, CA125 and stage, and the C-index was 0.820., Conclusion: Preoperative low HAR was associated with short-term survival in GC patients. The prognostic nomogram model can accurately predict the short-term survival of GC patients with D2 radical resection., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively improve impaired swallowing in Parkinson's disease (PD) patients with dysphagia. However, little is known about how rTMS affects the corresponding brain regions in this patient group. In this case-control study, we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy, Capital Medical University. The patients received high-frequency rTMS of the motor cortex once per day for 10 successive days. Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls. The results revealed that before treatment, PD patients with dysphagia showed greater activation in the precentral gyrus, supplementary motor area, and cerebellum compared with healthy controls, and this enhanced activation was weakened after treatment. Furthermore, before treatment, PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus, caudate nucleus, and left thalamus compared with healthy controls, and this activation increased after treatment. In addition, PD patients with dysphagia reported improved subjective swallowing sensations after rTMS. These findings suggest that swallowing function in PD patients with dysphagia improved after rTMS of the motor cortex. This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus. The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University (approval No. 2018bkky017) on March 6, 2018 and was registered with Chinese Clinical Trial Registry (registration No. ChiCTR 1800017207) on July 18, 2018., Competing Interests: None

The development of acid-resistant and efficient corrosion inhibitors is of great significance for metal protection in many industrial processes. In this work, eight cases of sandwich-type polyoxometalate (POM)-based inorganic-organic hybrids, namely, carboxyethyltin and transition metal (TM) cofunctionalized tungstoantimonates and tungstobismuthates, formulated as Na x K 10- x [(SnR) 2 (TM(H 2 O) 3 ) 2 (B-β-SbW 9 O 33 ) 2 ]· m H 2 O and Na y K 10- y [(SnR) 2 (TM(H 2 O) 3 ) 2 (B-β-BiW 9 O 33 ) 2 ]· n H 2 O (abbreviated as SbW 9 -TM-SnR and BiW 9 -TM-SnR ; TM = Mn, Co, Ni, and Zn; m = 18, 24, 24, and 22; n = 30, 25, 20, and 21; SnR = Sn(CH 2 CH 2 COO)) are first used as green corrosion inhibitors for 20 # carbon steel in 0.5-2.0 M HCl solutions. Weight loss and electrochemical experiments prove that the corrosion inhibition efficiency is all above 81% for these POM-based corrosion inhibitors at 150 mg L -1 , and SbW 9 -Mn-SnR shows the highest efficiency of 96.9% at 150 mg L -1 after immersion in a 0.5 M HCl solution for 10 h. Scanning electron microscopy-energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy analyses show that these POM-based inhibitors form films on the carbon steel and the adsorption mechanism obeys the Langmuir adsorption model. The thermodynamic activation parameters were calculated, proving the occurrence of both chemical and physical adsorptions. The film-forming mechanism was also analyzed. This work provides guidance for synthesizing new lacunary POM-based materials to protect metals from corrosion in HCl pickling., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

We aimed to illustrate the influence of N6-methyladenosine (m6A) long non-coding RNAs (lncRNAs) and immune cell infiltration in hepatocellular carcinoma (HCC). The relationship of lncRNAs and m6A was identified through gene expression analysis using PERL and R packages. The Kyoto Encyclopedia of Genes and Genomes gene expression enrichment analysis was performed via gene set enrichment analysis. Lasso regression was utilized to construct prognostic model. Differences in the tumor microenvironment and the immune correlation were analyzed to clarify immune cell infiltration in different clusters and their correlation with the clinical prognosis. Co-expression analysis showed that lncRNA expression was associated closely with m6A. Many lncRNAs were predictive risk factors of prognosis in HCC. m6A-lncRNAs were partially highly expressed in tumor tissue and could be used in a prognostic model to predict HCC prognosis, independent of other clinical characteristics. 'NOTCH SIGNALING PATHWAY' was most significantly enriched according to GSEA. CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) was overexpressed in tumor tissue. Immune cells, such as activated CD4 memory T cells, CD8 T cells, and follicular helper T cells, highly infiltrated tissues in cluster 2. All related scores were higher in cluster 2, indicating a lower purity of tumor cells and higher density of immune-related cells in the tumor microenvironment. m6A-lncRNAs are closely related to HCC occurrence and progression. Corresponding prognostic models can help predict HCC prognosis. m6A-lncRNAs and the related immune cell infiltration in the tumor microenvironment can provide novel therapeutic targets in HCC that need to be further studied.[Figure: see text].

The insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) pertain to a highly conservative RNA-binding family that works as a post-transcriptional fine-tuner for target transcripts. Emerging evidence suggests that IGF2BPs regulate RNA processing and metabolism, including stability, translation, and localization, and are involved in various cellular functions and pathophysiologies. In this review, we summarize the roles and molecular mechanisms of IGF2BPs in cancer development and progression. We mainly discuss the functional relevance of IGF2BPs in embryo development, neurogenesis, metabolism, RNA processing, and tumorigenesis. Understanding IGF2BPs role in tumor progression will provide new insight into cancer pathophysiology., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A new polyoxometalate (POM)-based organic-inorganic hybrid Cu-coordination polymer, namely {((Cu(bipy)) 2 ( μ -PhPO 3 ) 2 Cu(bipy)) 2 H(PCuW 11 O 39 )·3H 2 O} n (denoted as compound 1, bipy = 2,2'-bipyridine, PhPO 3 = phenylphosphonate), was self-assembled hydrothermally. Single-crystal X-ray diffraction (SC-XRD) analysis shows that two unique types of 1D chains are present in compound 1, i.e. Cu(II)-organophosphine and organonitrogen complex cation ([((Cu(bipy)) 2 ( μ -PhPO 3 ) 2 Cu(bipy)) 2 ] 4+ ) chains and Cu-monosubstituted Keggin-type polyoxoanion ([PCuW 11 O 39 ] 5- ) chains, forming a hetero-POM. Crystalline compound 1 as a new enzyme immobilization support exhibited a high horseradish peroxidase (HRP) loading capacity (268 mg g -1 ). The powder X-ray diffraction (PXRD), FTIR, zeta potential, confocal laser scanning microscopy (CLSM) and circular dichroism (CD) results show that HRP is only immobilized on the surface of compound 1 through simple physical adsorption without a secondary structure change. This POM-immobilized enzyme (HRP/1) was first used for degradation of pollutants in wastewater, and it showed a high degradation efficiency and TOC removal efficiency for phenol, 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP) within 30 min reaction time. Moreover, HRP/1 exhibited better operational and storage stabilities and reusability compared with free HRP. This work suggests that POMs can be used as new supports for enzyme immobilization and POM-immobilized enzymes may be used as a new kind of biocatalyst for degradation of phenolic pollutants.