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Abstract The brown planthopper (BPH) is one of the most problematic pests affecting rice (Oryza sativa L.) yields in Asia. Breeding rice varieties containing resistance genes is the most economical and effective means of controlling BPH. In this study, the key factors in resistance to BPH were investigated between the high-resistance rice variety “R26” and the susceptible variety “TN1” using RNA-sequencing. We identified 9527 differentially expressed genes (DEGs) between the rice varieties under BPH-induced stress. Weighted time-course gene co-expression network analysis (WGCNA) indicated that the increased expression of genes is associated with plant hormones, MAPK signaling pathway and biosynthesis of other secondary metabolites, which were involved in disease resistance. A connection network identified a hub gene, OsREM4.1 (BGIOSGA024059), that may affect rice resistance to the BPH. Knocking out OsREM4.1 in rice can lead to a decrease in callose, making it less resistant to BPH. Overall, the expression of differentially expressed genes varies among rice varieties with different resistance in BPH invasion. Inaddition, R26 enhances resistance to BPH by upregulating genes and secondary metabolites related to stress resistance and plant immunity. In summary, our study provides valuable insights into the genome-wide expression profile of DEGs in rice under BPH invasion through high-throughput sequencing, and further suggests that R26 can be used to develop high resistance rice lines in BPH resistant breeding programs.

ObjectiveTo analyze the clinical prognostic factors and treatments for angioimmunoblastic T-cell lymphoma (AITL) and develop a novel prognostic model specifically for AITL.MethodWe retrospectively analyzed 231 patients with AITL from the First Affiliated Hospital of Zhengzhou University. Patients were enrolled between January 2014 and July 2023. The primary end points were overall survival (OS) and progression-free survival (PFS).ResultThe patients’ median age was 63 years, with 88.3% at an advanced stage (III/IV). The majority of patients (47.6%) received anthracycline-containing regimens, and there was no significant difference in survival compared with those treated with epigenetic-targeting and gemcitabine- containing regimens. The median PFS and OS were 6 and 17 months, respectively. In multivariate analysis, age >60 years, Eastern Cooperative Oncology Group performance status ≥2, elevated LDH, and splenomegaly were associated with inferior OS. Based on these four factors, a novel prognostic model (AITL model) was constructed that stratified patients into low‐, intermediate‐, and high‐risk groups, with 2-year OS estimates of 63.6%, 42.1%, and 18.6%, respectively.ConclusionCurrently, there is no consensus on the optimal initial therapy for AITL, and the efficacy of anthracycline-containing regimens remains suboptimal. The novel model developed herein demonstrates predictive significance for both OS and PFS, and exhibits better stratification and discrimination capabilities.

Objective To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model. Methods PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery. Results The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material. Conclusion PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

Abstract High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of ovarian cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates from drug-tolerant persister (DTP) cells. We generated isogenic clones of treatment-naïve and cisplatin-tolerant persister HGSOC cells. In addition, single-cell RNA sequencing of barcoded cells was performed in a xenograft model with HGSOC cell lines after platinum-based therapy. Published single-cell RNA-sequencing data from neo-adjuvant and non-treated HGSOC patients and patient data from TCGA were analyzed. DTP-derived cells exhibited morphological alterations and upregulation of epithelial-mesenchymal transition (EMT) markers. An aggressive subpopulation of DTP-derived cells showed high expression of the stress marker ATF3. Knockdown of ATF3 enhanced the sensitivity of aggressive DTP-derived cells to cisplatin-induced cell death, implying a role for ATF3 stress response in promoting a drug tolerant persister cell state. Furthermore, single cell lineage tracing to detect transcriptional changes in a HGSOC cell line-derived xenograft relapse model showed that cells derived from relapsed solid tumors express increased levels of EMT and multiple endoplasmic reticulum (ER) stress markers, including ATF3. Single cell RNA sequencing of epithelial cells from four HGSOC patients also identified a small cell population resembling DTP cells in all samples. Moreover, analysis of TCGA data from 259 HGSOC patients revealed a significant progression-free survival advantage for patients with low expression of the ATF3-associated partial EMT genes. These findings suggest that increased ATF3 expression together with partial EMT promote the development of aggressive DTP, and thereby relapse in HGSOC patients.

To enhance our understanding of Aspergillus cristatus, an important functional microorganism, the characteristics of its mitochondrial genome were analyzed and compared with related species. The mitochondrial genome of A. cristatus was determined to be 77,649 bp in length, with 15 protein-coding regions. Notably, its length surpassed that of the other species, primarily attributable to the intron length. Gene order exhibited significant variations, with greater conservation observed in the genus Penicillium compared to Aspergillus. Phylogenetic tree analyses indicated that the genera Aspergillus and Penicillium are closely related but monophyletic. Furthermore, the phylogenetic tree constructed based on protein-coding genes effectively distinguished all strains with high branching confidence. This approach provides a robust reflection of the evolutionary relationship between A. cristatus and its related species, offering potential for the development of molecular markers suitable for Aspergillus and Penicillium.

Abstract Objective The clinical characteristics of hospitalized children with acute poisoning were analyzed to provide a reference for preventing poisoning and seeking effective prevention and treatment. Methods The clinical data of 112 children with acute poisoning admitted to Qilu Hospital of Shandong University from January 1, 2018, to December 31, 2021, were collected and analyzed from different perspectives. Results The majority of acute poisoning cases that occurred in children were in early childhood and preschool age (89 cases, accounting for 79.4%). The most common types of poisoning were pesticide poisoning and drug poisoning, and the main ways of poisoning were accidental administration via the digestive tract and accidental ingestion. Poisoning occurred slightly more in spring and summer all year round, and most children had a good prognosis after timely treatment. Conclusion Acute poisoning often occurs in children. Parental education and intensified child supervision are needed to prevent the incidence of unintentional poisoning.

Abstract Background Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. Methods The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (

ABSTRACTObjective To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK).Methods We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022.Results Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein–Barr virus (EBV) expression. The 5-years overall survival rate was 83%.Conclusion Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.

BackgroundParkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.ObjectiveDetermine the correlation between the time of dopaminergic replacement treatment initiation and the severity of clinical symptoms in PD, including motor and non-motor symptoms.MethodsPD patients were divided between 155 people who were diagnosed de novo and 165 PD patients receiving dopamine replacement therapy. Basic patient characteristics included gender, age, age at onset, disease duration, and the time of dopaminergic replacement treatment initiation. We used MDS-UPDRS scores to evaluate the severity of motor symptoms and we also used the scale to assess the severity of non-motor symptoms such as cognition, mood, sleep, and quality of life.ResultsThe mean time between symptom onset and the initiation of drug treatment was 31.0 (22.5) months. After adjusting for age, sex, age at onset, and disease duration, we found that the MDS-Unified Parkinson's Disease Rating Scale (UPDRS)-III score increased faster in the de novo group with a similar disease duration (F = 8.7, p = 0.0034) than the treatment group. The cumulative incidence of progression to H-Y score 3 in de novo PD group over disease duration was 39.7% in 50months and 92.2% in 100 months, while in treated group such cumulative incidence was 15.5% in 50 months, 51.4% in 100 months and 81.5% in 150 months. The cumulative incidence of patients in the de novo PD group was higher than that in the treated group (p = 0.001), suggesting that untreated patients were more likely to progress to the advanced stages. Symptoms onset, the time between symptom onset and treatment initiation, age, sex, and disease duration explained 28.95% of the total variation in the MDS-UPDRS-III score for motor symptoms. In drug-naïve patients, the time between symptom onset and treatment initiation explained 20.1% of the total variation in the MDS-UPDRS-III score for motor symptoms (t = 6.15, p < 0.001).ConclusionsThese data in our study showed that early dopaminergic replacement treatment have played a positive role in PD patients, while dopaminergic replacement delayed treatment might be detrimental to motor symptoms and non-motor state of PD patient. Recognizing early stage symptoms of PD and early diagnosis are of great significance to treatment.

Abstract The aim of this research was to determine the residues of dioxins and dioxin-like polychlorinated biphenyls in cultured eel and find out the source of pollution and the distribution pattern of eels. One hundred samples of eel, 4 fodder samples, and 12 environmental samples (water, plants, and soil) were collected from 4 cities and counties in Jiangxi Province, China. The contents of 17 kinds of dioxins (PCDD/Fs) and 12 kinds of dioxin-like polychlorinated biphenyls (dl-PCBs) were determined by high-resolution gas chromatography-tandem mass spectrometry, and the exposure risk was evaluated by using risk index. The total toxicity equivalence quantity (TEQ) of dioxin and dioxin-like polychlorinated biphenyls in eel and fodder samples collected in the study area were 0.65 ± 0.31 pg/g and 0.10 ± 0.02 pg/g, respectively. Dl-PCBs were the main dioxin pollution in eel and fodder samples. 2,3',4,4',5-pentachlorodiphenyl and 2,3,3',4,4'-pentachlorobiphenyl were the main contributing monomers. The environmental samples were mainly polluted by polychlorinated dibenzo-p-dioxins (PCDDs), with the main contributing monomer being Octachlorodibenzodioxins (OCDD), while 3,3',4,4',5-pentachlorobiphenyl and 2,3,4,7,8-pentachlorodibenzofuran were the main toxic compounds in eel and fodder. The dioxin pollution of eels cultured in Jiangxi Province was mainly from fodder polluted via dl-PCBs. The meat segment VI (tail) exhibited a strong enrichment effect of polychlorinated benzofurans (PCDFs). It should be the key part for dioxins and dioxin-like polychlorinated biphenyls assessment. Further, the results were helpful to improve the edible safety of eel products and the efficiency of the risk assessment of dioxins and dioxin-like polychlorinated biphenyls in fish. Graphical Abstract

Abstract Background The coronavirus disease (COVID-19) pandemic has seriously impacted the mental and sexual health of the general population. Patients dealing with infertility constitute a unique subset within society, susceptible to heightened sensitivity amid pressures and crises. However, to the best of our knowledge, the impact of the different stages of the COVID-19 pandemic on the mental and sexual health of patients with infertility has not been investigated. Therefore, this study aimed to investigate the mental and sexual health of patients with infertility during different stages of the COVID-19 pandemic (during the lockdown, when controls were fully liberalized, and during the post-pandemic era). Methods This prospective before-and-after study was conducted between April and May 2022 (during the lockdown), December and January 2023 (when controls were fully liberalized), and May and August 2023 (during the post-pandemic era). This study explored the sexual and mental health of women with infertility during the three stages of the COVID-19 pandemic using standardized mental health and sexual function questionnaires. The Chi-square test was used to compare categorical data, and the ANOVA test was used to compare numerical data. Results Patients had the highest 7-item Generalized Anxiety Disorder Scale (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9) scores and the highest rates of anxiety and depression during the immediate full-release phase. During the complete liberalization phase, patients had the lowest Female Sexual Function Index (FSFI) scores and the highest incidence of sexual dysfunction. Conclusion This study is the first one to report the repercussions of COVID-19 on the mental and sexual well-being of individuals experiencing infertility across various phases of the pandemic. Upon the complete lifting of control measures, close to 99% of participants exhibited varying degrees of anxiety and depression. Our research underscores that individuals with infertility faced elevated levels of anxiety, depression, and sexual dysfunction during the phase of full liberalization of COVID-19 control measures, in stark contrast to the periods of lockdown and the post-pandemic era.

Background Triglyceride-glucose (TyG) index is an index to evaluate insulin resistance (IR) and obesity-related metabolic diseases, which is closely related to the high risk of cardiovascular disease (CVD). However, TyG index may be different from the high risk of CVD in middle-aged obese people of different genders. Objective To investigate the relationship between TyG index and the high risk of CVD in middle-aged obese people of different genders, and to evaluate its role in the prevention and treatment of CVD. Methods A total of 30 425 middle-aged obese residents were selected from 10 early screening and comprehensive intervention projects of high-risk CVD population in Anhui Province and investigated by investigators who were trained and qualified, using the preliminary screening questionnaire and basic information registration form designed by the National Cardiovascular Center. The main survey contents included gender, age, hypertension, dyslipidemia, diabetes, smoking and alcohol consumption, etc, and perform a CVD high-risk assessment. The included residents were divided into the male group (n=11 566) and female group (n=18 859). The male group was divided into T1 (7.417-8.870) (n=2 892), T2 (8.871-9.204) (n=2 891), T3 (9.205-9.578) (n=2 892) and T4 (9.579-11.435) (n=2 891) subgroups, the female group was divided into F1 (7.579-8.876) (n=4 715), F2 (8.877-9.183) (n=4 720), F3 (9.184-9.526) (n=4 710) and F4 (9.527-11.647) (n=4 714) subgroups according to the quartiles of TyG index. Binary Logistic regression analysis was used to explore the relationship between TyG index and the high risk of CVD, and Z-test was used to compare the differences in effect values among subgroups. Results The high risk rate of CVD was 28.4% (3 280/11 566) in the male group and 26.0% (4 909/18 859) in the female group. Binary Logistic regression analysis showed that TyG index T2 (F2), T3 (F3), T4 (F4) in male group (female group) were correlated with the high risk of CVD (P

Abstract Objective This study aimed to explore metabolic abnormalities in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) for metabolism-related genes. Methods We downloaded expression data for metabolism-related genes, performed differential expression analysis, and applied weighted gene co-expression network analysis (WGCNA) to identify metabolism-related functional modules. We obtained normalised miRNA expression data and identified master methylation regulators for metabolism-related genes. Cox regression of data on metabolism-related genes was performed to screen for genes that affect the prognosis of patients with CESC. Furthermore, we selected key genes for validation. Results Our results identified 3620 metabolism-related genes in CESC, 2493 of which contained related mutations. The co-occurrence of CUBN, KALRN, and HERC1 was related to the prognosis of CESC. The fraction of genome altered (FGA) closely correlated with overall survival. In expression analysis, 374 genes were related to the occurrence and prognosis of CESC. We then identified four metabolic pathway modules in WGCNA. Further analysis revealed that glycolysis/gluconeogenesis was related to endothelial cells and that arachidonic acid metabolism was related to cell proliferation. These four modules were also related to the prognosis of CESC. Among CESC-related metabolic genes, two genes were found to be regulated by microRNAs (miRNAs) and methylation, whereas another two genes were coregulated by miRNAs and mutations. Conclusions Among metabolism-related genes, 15 genes were related to the prognosis of CESC. The co-occurrence of CUBN/KALRN/HERC1 was associated with CESC prognosis. Glycolysis/gluconeogenesis was related to endothelial cells, and arachidonic acid metabolism was related to cell proliferation.

Abstract Background To date, there is no consensus on whether intrauterine insemination (IUI) treatment is required in young patients with diminished ovarian reserve (DOR). Pregnancy outcomes in young DOR patients undergoing IUI are controversial. The existing studies are all single-center studies, with no existing multicenter cohort studies. The purpose of this multicenter study was to investigate the pregnancy outcomes of young DOR patients undergoing IUI. Methods This multicenter cohort study included a total of 4600 cycles in 2204 infertile patients who underwent IUI treatment in three reproductive medical centers between September 2018 and January 2022. The research subjects were divided into two groups according to their serum anti-Müllerian hormone (AMH) levels. Propensity score matching (PSM) was used to match the research subjects at a ratio of 1:4. The pregnancy outcomes in the two groups were compared. Results There was no significant difference in the clinical pregnancy rates (CPR), biochemical rates, and ectopic pregnancy rates between the two groups (P > 0.05). There were, however, significant differences in the miscarriage rates between the groups (P

Abstract Purpose The prognostic factors for diffuse large B‐cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. Methods We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. Results In all patients with bulky mass DLBCL, the 1‐year and 3‐year OS rates were 72.7% and 57.1%, respectively, and the 1‐year and 3‐year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression‐free survival (PFS; p = 0.001) than the non‐MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3–5 (OS: p = 0.011; PFS: p

Abstract Objective Carbon ion radiotherapy (C-ion RT) for chordomas has been gradually performed in several research centres. This study aimed to systematically review the results of clinical reports from these institutions and to evaluate the safety and efficacy of C-ion RT. Methods In accordance with the PRISMA guidelines and set search strategies, we searched four databases for articles from their inception to February 11, 2023. These articles were screened, and data were extracted independently by two researchers. STATA 14.0 was used for statistical analysis of survival results. Results A total of 942 related articles were retrieved, 11 of which were included. Regarding lesion location, 57% (n = 552) originated in the sacral region, 41% (n = 398) in the skull base, and 2% (n = 19) in the spine (upper cervical). The local control (LC) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 96%, 93%, 83%, 76%, 71%, and 54%, respectively. The overall survival (OS) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 99%, 100%, 93%, 85%, 76%, and 69%, respectively. Acute and late toxicities were acceptable, acute toxicities were mainly grade 1 to grade 2 and late toxicities were mainly grade 1 to grade 3. Conclusion C-ion RT has attractive clinical application prospects and is an important local treatment strategy for chordomas. Encouraging results were observed in terms of LC and OS. Meanwhile, the acute and late toxicities were acceptable. PROSPERO registration number: CRD42023398792.

Abstract Background Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. Methods For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. Results Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7–26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01–54.84; P

To solve the problem of incomplete cleaning of dust filter cartridge, the effect of the installation of diffuser and venture-tube on the pulsed-jet performance for dust cleaning filter cartridge was experimentally investigated. The effects of the jet distance on the pulse-jet pressure, the pulsed-jet intensity and uniformity were analyzed. The evolution of the filtration resistance during the stages of dust filtration and cleaning operation were compared. The results show that both diffuser and venture-tube could promote the pulse jet to expand and achieve a more uniform jet flow, but the combination of the diffuser and venture-tube would increase the airflow resistance, resulting in a lower pulsed-jet pressure. The pulsed-jet intensity increased first and then decreased with the jet distance under the conditions of common jet, the diffuser or the venture-tube installed only. When the jet distance was lower than 200 mm, the addition of diffuser and venture-tube alone or in combination is beneficial to improve the uniformity of injection. The best performance was achieved under the condition of 100 mm jet distance and the diffuser install only, with filtration period 1.3 times longer than that under the common pulse jet cleaning condition.

Abstract Background There is an urgent need for effective treatment of patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R‐DLBCL). This trial investigated the efficacy of decitabine in combination with rituximab, cisplatin, cytarabine, dexamethasone (RDHAP) in R/R‐DLBCL. Methods 56 patients were divided into two groups (decitabine‐RDHAP group. n = 35; RDHAP group, n = 21). The primary endpoints were the overall response rate (ORR) and duration of remission (DOR). Secondary objectives were toxicity, progression‐free survival (PFS), and overall survival (OS). Results The ORR was 40% and 33% for decitabine‐RDHAP and RDHAP groups, respectively, with no difference between the groups. The DOR for the decitabine‐RDHAP regimen was higher than that for the RDHAP regimen (p = 0.044). After a median follow‐up of 12.0 months, the median PFS and OS were 7.0 and 17.0 months for in the decitabine‐RDHAP group and 5.0 and 9.0 months in the RDHAP group with no significant differences between the two groups (p = 0.47, 0.17). The incidence of adverse events was not significantly different between groups. Conclusion The decitabine‐RDHAP regimen is effective and well tolerated, and is a promising salvage regimen for R/R‐DLBCL.

Abstract Objective To explore the preoperative influential factors of difficult thyroidectomy and establish a preoperative nomogram for predicting the difficulty of thyroidectomy. Methods A total of 753 patients who underwent total thyroidectomy with central lymph node dissection between January 2018 and December 2021 were retrospectively enrolled in this study and randomly divided into training and validation groups at a ratio of 8:2. In both subgroups, the patients were divided into difficult thyroidectomy and nondifficult thyroidectomy groups based on the operation time. Patient age, sex, body mass index (BMI), thyroid ultrasound, thyroid function, preoperative fine needle aspiration (FNA), postoperative complications and other data were collected. Logistic regression analysis was performed to identify the predictors of difficult thyroidectomy, and a nomogram predicting surgical difficulty was created. Results Multivariate logistic regression analysis demonstrated that male sex (OR = 2.138, 95% CI 1.055–4.336, p = 0.035), age (OR = 0.954, 95% CI 0.932–0.976, p

Abstract The repressor element 1 silencing transcription factor (REST) has been proposed to function as a transcription factor to silence gene transcription by binding to repressor element 1 (RE1), a highly conserved DNA motif. The functions of REST in various tumors have been studied, but its role and correlation with immune cell infiltration remains uncertain in gliomas. REST expression was analyzed in datasets of The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) and validated by the Gene Expression Omnibus and Human Protein Atlas databases. The clinical prognosis of REST was evaluated by clinical survival data of TCGA cohort and validated by Chinese Glioma Genome Atlas cohort. MicroRNAs (miRNAs) contributing to REST overexpression in glioma were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. The correlations between immune cell infiltration level and REST expression were analyzed by TIMER2 and GEPIA2 tools. Enrichment analysis of REST was performed using STRING and Metascape tools. The expression and function of predicted upstream miRNAs at REST and their association with glioma malignancy and migration were also confirmed in glioma cell lines. REST was highly expressed and associated with poorer overall survival and disease-specific survival in glioma and some other tumors. MiR-105-5p and miR-9-5p were identified as the most potential upstream miRNAs of REST in glioma patient cohort and experiments in vitro. REST expression was positively correlated with infiltration of immune cells and the expression of immune checkpoints such as PD1/PD-L1 and CTLA-4 in glioma. Furthermore, histone deacetylase 1 (HDAC1) was a potential REST-related gene in glioma. Enrichment analysis of REST found chromatin organization and histone modification were the most significant enriched terms, and Hedgehog-Gli pathway might be involved in the effect of REST on the pathogenesis of glioma. Our study suggests REST to be an oncogenic gene and the biomarker of poor prognosis in glioma. High REST expression might affect the tumor microenvironment of glioma. More basic experiments and large clinical trials aimed at the carcinogenetic study of REST in glioma will be needed in the future.

Abstract Objective This study aimed to evaluate and conduct a meta-analysis on the efficacy and safety of proton beam therapy (PBT) for rhabdomyosarcoma (RMS). Methods We searched for articles using PubMed, Embase, Cochrane Library, and Web of Science databases from their inception to December 22, 2022. Two researchers independently screened literature and extracted data. Statistical analyses were performed using STATA version 14.0. Results We got 675 candidate articles, of which 11 studies were included in our study according to the inclusion and exclusion criteria. Of the 544 RMS patients who received PBT. The local control (LC) rate at 1, 2, 3, 4, and 5 years were 96% (95% confidence interval (CI) 0.91–1.01), 93% (95% CI 0.86–1.00), 78% (95% CI 0.71–0.85), 85% (95% CI 0.78–0.92), and 84% (95% CI 0.74–0.95), respectively. The progression-free survival (PFS) rate at 1, 2, 3, 4, and 5 years were 82% (95% CI 0.72–0.92), 73% (95% CI 0.61–0.84), 63% (95% CI 0.47–0.79), 64% (95% CI 0.54–0.74), and 76% (95% CI 0.59–0.94), respectively. The overall survival (OS) rate at 1, 2, 3, 4, and 5 years were 93% (95% CI 0.86–1.00), 85% (95% CI 0.76–0.95), 80% (95% CI 0.63–0.96), 71% (95% CI 0.62–0.80), and 82% (95% CI 0.71–0.94), respectively. Acute and late toxicities were mainly grades 1 to 2 in all studies. Conclusion As an advantageous RT technique, PBT is an emerging option for patients with RMS, particularly children and adolescents patients. The data showed that PBT is a feasible, safe, and effective modality for RMS, showing promising LC, OS, PFS, and lower acute and late toxicities. PROSPERO registration number: CRD42022329154.

Abstract High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1–2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity‐modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.

The electrochemical splitting of water into hydrogen and oxygen is considered one of the most promising approaches to generate clean and sustainable energy. However, the low efficiency of the oxygen evolution reaction (OER) acts as a bottleneck in the water splitting process. Herein, interface engineering heterojunctions between ZIF-67 and layered double hydroxide (LDH) are designed to enhance the catalytic activity of the OER and the stability of Co-LDH. The interface is built by the oxygen (O) of Co-LDH and nitrogen (N) of the 2-methylimidazole ligand in ZIF-67, which modulates the local electronic structure of the catalytic active site. Density functional theory calculations demonstrate that the interfacial interaction can enhance the strength of the Co-Oout bond in Co-LDH, which makes it easier to break the H-Oout bond and results in a lower free energy change in the potential-determining step at the heterointerface in the OER process. Therefore, the Co-LDH@ZIF-67 exhibits superior OER activity with a low overpotential of 187 mV at a current density of 10 mA cm-2 and long-term electrochemical stability for more than 50 h. This finding provides a design direction for improving the catalytic activity of OER.

Background: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. Methods: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Results: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Conclusion: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

The thermoelectric transport properties of four kinds of DNA bases sandwiched between two zigzag-edge graphene nanoribbon electrodes are investigated by first-principles calculation. The modulation of quantum interference, molecular length, and molecular torsion on thermoelectric transport properties are studied. It is found that the thermopower and efficiency can be obviously enhanced in the guanine and electrode coupling geometry that manifests a quantum interference effect. A decrease of thermopower with a number of DNA bases has been found, while the efficiencies have a different trend with the increase of the number of different molecules. In addition, the thermopower and efficiency also can be considerably enhanced by the twisting angle between the molecule and graphene electrodes.

Organic frameworks (OFs) offer a novel strategy for assembling organic semiconductors into robust networks that facilitate transport, especially the covalent organic frameworks (COFs). However, poor electrical conductivity through covalent bonds and insolubility of COFs limit their practical applications in organic electronics. It is known that the two-dimensional intralayer π∙∙∙π transfer dominates transport in organic semiconductors. However, because of extremely labile inherent features of noncovalent π∙∙∙π interaction, direct construction of robust frameworks via noncovalent π∙∙∙π interaction is a difficult task. Toward this goal, we report a robust noncovalent π∙∙∙π interaction-stacked organic framework, namely πOF, consisting of a permanent three-dimensional porous structure that is held together by pure intralayer noncovalent π∙∙∙π interactions. The elaborate porous structure, with a 1.69-nm supramaximal micropore, is composed of fully conjugated rigid aromatic tetragonal-disphenoid-shaped molecules with four identical platforms. πOF shows excellent thermostability and high recyclability and exhibits self-healing properties by which the parent porosity is recovered upon solvent annealing at room temperature. Taking advantage of the long-range π∙∙∙π interaction, we demonstrate remarkable transport properties of πOF in an organic-field-effect transistor, and the mobility displays relative superiority over the traditional COFs. These promising results position πOF in a direction toward porous and yet conductive materials for high-performance organic electronics.

Over 170 years after the infamous Irish Potato Famine, potato late blight (PLB) caused by Phytophthora infestans remains the single most devastating disease of global potato production, causing up to 10 billion USD in yield loss and management costs. Through decades of research, growers and agronomists in the field as well as laboratory scientists have made significant progress in understanding the molecular pathogenesis process of this critical pathosystem and effective management strategies to control PLB. Yet, the need to feed an ever-increasing global population under changing climate demands continued improvement in efficient and sustainable PLB management schemes that can be implemented across a broad economic spectrum. In this review, we briefly summarize the current understanding of the molecular interaction between P. infestans and its host plants, highlight the current integrated pest management strategy to control PLB on local and continental scales, and discuss the potential of further improvement of sustainable PLB control through genetic enhancement of crop resistance and emerging crop protection technologies.

LATS1 is reported to regulate the transition of luminal-basal-like cell plasticity in breast cancer. Here the authors report that LATS1 limits the progression of luminal breast cancer by associating with NCOR1 nuclear corepressor to repress ERα-downregulated genes in luminal cells.

Abstract Objective This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. Methods We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0. Results We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961–1.009, I 2 = 0%), 85.8% (95% CI = 0.687–1.030, I 2 = 91%), 86% (95% CI = 0.763–0.957, I 2 = 85.3%), 91.1% (95% CI = 0.849–0.974), 74.3% (95% CI = 0.666–0.820, I 2 = 85.2%), and 64.7% (95% CI = 0.451–0.843, I 2 = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995–1.004, I 2 = 0%), 89.6% (95% CI = 0.811–0.980, I 2 = 96.6%), 85% (95% CI = 0.750–0.950, I 2 = 89.4%), 92.4% (95% CI = 0.866–0.982), 72.7% (95% CI = 0.609–0.844, I 2 = 95.3%), and 72.1% (95% CI = 0.661–0.781, I 2 = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively. Conclusion As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity. PROSPERO registration number CRD42021258480.

Objective To investigate the therapeutic effect of preoperative ureteral stenting on the treatment of renal or upper ureteral calculi with flexible ureteroscopic lithotripsy. Methods From October 2018 to July 2021, 256 patients who had undergone flexible ureteroscopic lithotripsy for renal or upper ureteral calculi in Beijing Haidian Hospital were retrospectively selected. According to whether the patients accepted preoperative ureteral stenting or not, the patients were divided into experimental group (n=192) and control group (n=64), and the experimental group was further divided into long-(14 d, n=64) and short-term (7 d, n=128) group according to the time of preoperative ureteral stenting. The differences in success rate of surgery, operative time, amounts of intraoperative blood loss, length of hospital-stay, incidence of postoperative complications and stone-free rate were analyzed to evaluate the therapeutic effects. Results The operative time and intraoperative blood loss of the control group were significantly higher than that of the experimental group, there was significant difference between the two groups(P＜0.001). The long-term group had longer hospital-stay time (P＜0.001), shorter operative time and less amounts of blood loss (P＜0.001). The success rate of surgery and stone-free rate of the control group were lower than that of the experimental group (P＜0.05), while incidence of postoperative complications was higher than experimental group (P＜0.001). There was no significant difference between the short- and long-term group in the stone-free rate, while the postoperative complications of the short-term group was higher than the experimental group (P＜0.05). Conclusions Preoperative ureteral stenting improves the success rate of surgery operation and the stone-free rate, reduces the postoperative complications and intraoperative blood loss, shorten the operative time.

The diversity of root endophytic microorganisms, which is closely related to plant life activities, is known to vary with the plant growth stage. This study on the ratooning rice Jiafuzhan explored the diversity of the root endophytic bacteria and fungi and their dynamics during the plant life cycle. By sequencing the 16S ribosomal ribonucleic acid (16S rRNA) and internal transcribed spacer (ITS) genes, 12,154 operational taxonomic units (OTUs) and 497 amplicon sequence variants (ASVs) were obtained, respectively. The root endophytic microorganisms of rice in the seedling, tillering, jointing, heading, and mature stages of the first crop and at 13, 25, and 60 days after regeneration (at the heading, full heading, and mature stages of the second crop, respectively) were analyzed using diversity and correlation analyses. There were significant differences in the α-diversity and β-diversity of root endophytic bacteria and fungi in the growth stage. Additionally, linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed biomarker bacteria for each growth stage, but biomarker fungi did not exist in every stage. Moreover, the correlation analysis showed that the bacterial and fungal biomarkers interacted with each other. Furthermore, the nitrogen-fixing genus Bradyrhizobium existed in all growth stages. These findings indicate the pattern of root endophytic microorganisms of ratooning rice at different growth stages, and they provide new insights into the high yield of the second crop of ratooning rice (in light of the abundance of various bacteria and fungi).

ABSTRACT Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

Most plants belonging to the widely distributed genus Dianthus are used for gardening. Interspecific hybridization of different Dianthus species leads to blurred genetic backgrounds. To obtain more genomic resources and understand the phylogenetic relationships among Dianthus species, the chloroplast genomes of 12 Dianthus species, including nine Dianthus gratianopolitanus varieties, were analyzed. The chloroplast genomes of these 12 species exhibited similar sizes (149,474–149,735 bp), with Dianthus caryophyllus having a chloroplast genome size of 149,604 bp marked by a significant contraction in inverted repeats. In the chloroplast genome of Dianthus, we identified 124–126 annotated genes, including 83–84 protein-coding genes. Notably, D. caryophyllus had 83 protein-coding genes but lacked rpl2. The repeat sequences of the chloroplast genome were consistent among species, and variations in the sequence were limited and not prominent. However, notable gene replacements were observed in the boundary region. Phylogenetic analysis of Dianthus indicated that D. caryophyllus and D. gratianopolitanus were most closely related, suggesting that the degree of variation within nine Dianthus varieties was no less than the variation observed between species. These differences provide a theoretical foundation for a more comprehensive understanding of the diversity within Dianthus species.

As a major greenhouse gas, the continuous increase of carbon dioxide (CO2) in the atmosphere has caused serious environmental problems, although CO2 is also an abundant, inexpensive, and nontoxic carbon source. Here, we use metal-organic framework (MOF) with highly ordered hierarchical structure as adsorbent and catalyst for chemical fixation of CO2 at atmospheric pressure, and the CO2 can be converted to the formate in excellent yields. Meanwhile, we have successfully integrated highly ordered macroporous and mesoporous structures into MOFs, and the macro-, meso-, and microporous structures have all been presented in one framework. Based on the unique hierarchical pores, high surface area (592 m2/g), and high CO2 adsorption capacity (49.51 cm3/g), the ordered macroporous-mesoporous MOFs possess high activity for chemical fixation of CO2 (yield of 77%). These results provide a promising route of chemical CO2 fixation through MOF materials.

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