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Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Abstract Background Emerging evidence has indicated a link between the gut microbiota and acute lymphoblastic leukaemia (ALL). However, the acute changes in gut microbiota during chemotherapy and the predictive value of baseline gut microbiota in infectious complication remain largely unknown. Methods Faecal samples (n = 126) from children with ALL (n = 49) undergoing induction chemotherapy were collected at three timepoints, i.e., initiation of chemotherapy (baseline, T0), 7 days (T1) and 33 days (T2) after initiation of chemotherapy. Gut microbiome profile was performed via metagenomic shotgun sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 3 and HUMAnN) was performed to assign taxonomy and functional annotations. Gut microbiome at T0 were used to predict infection during chemotherapy. Results The microbial diversities and composition changed significantly during chemotherapy, with Escherichia coli, Klebsiella pneumoniae and Bifidobacterium longum being the most prominent species. The microbial metabolic pathways were also significantly altered during chemotherapy, including the pathway of pyruvate fermentation to acetate and lactate, and assimilatory sulfate reduction pathway. The receiver operating characteristic (ROC) models based on Bifidobacterium longum at T0 could predict infectious complications during the first month of chemotherapy with the area under the curve (AUC) of 0.720. Conclusions Our study provides new insights into the acute changes in microbial and functional characteristics in children with ALL during chemotherapy. The baseline gut microbiota could be potential biomarkers for infections during chemotherapy. Trial registration The study was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (2021-KY-171-01) and registered on http://www.chictr.org.cn (ChiCTR2200065406, Registration Date: November 4, 2022).

Purpose: This study represents a prospective phase I clinical research to verify the effectiveness and reliability of hydrogel application in Chinese cervical cancer patients. Materials and Methods: Eight patients were enrolled in the study. After completing intensity-modulated radiotherapy at 50.4 Gy/28 fractions, a 10 mL injection of hydrogel was administered to each patient through the posterior vaginal fornix under CT-guidance. Image-guided brachytherapy under CT or MRI guidance was given with a target dose of 6 Gy in 5 fractions to the high-risk clinical target volume. Rectal, sigmoid colon, and bladder D2cm3 were recorded for each brachytherapy. MRI scans were performed to measure the distance between the rectum and the cervix or tumor, as well as the spacer gel volume. Patients’ QLQ-C30 and QLQ-CX24 scores were recorded to assess treatment outcomes, and all adverse events were documented. Results: Among the eight patients, the average D2cc was 60.9 ± 3.4 Gy for the rectum, 64.7 ± 6.8 Gy for sigmoid colon and 77.1 ± 7.4 Gy for bladder, respectively. The distance between the cervix and rectum significantly increased after gel injection. None of the eight patients experienced grade 3 or higher acute toxic reactions during brachytherapy. None patient experienced late rectal toxicity. No adverse events definitively associated with the hydrogel were observed. Patients’ subjective quality of life scores did not significantly change before and after gel injection. The reduction ro the volume of the hydrogel were observed during the 24 to 36 weeks after injection. Conclusion: The application of the hydrogel effectively increased the distance between the cervix and rectum in brachytherapy for cervical cancer, limiting the rectal dose without increasing doses to other critical organs. In the short term, no severe adverse events were observed, indicating the safety and reliability of this approach. Further research is warranted to confirm its long-term safety and effectiveness.

Abstract Background During the COVID-19 epidemic in China, clinical nurses are at an elevated risk of suffering fatigue. This research sought to investigate the correlation between dispositional mindfulness and fatigue among nurses, as well as the potential mediation role of sleep quality in this relationship. Methods This online cross-sectional survey was performed from August to September 2022 to collect data from 2143 Chinese nurses after the re-emergence of COVID-19. The significance of the mediation effect was determined through a bootstrap approach with SPSS PROCESS macro. Results Higher levels of dispositional mindfulness were significantly negatively related to fatigue (r = -0.518, P

Background and aimsLiver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer’s disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study.MethodsIndependent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer’s disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses.ResultsMultivariable MR analysis showed causal association between Alzheimer’s disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer’s disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer’s disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer’s disease, and LIHC susceptibility.ConclusionsA significant causal relationship exists between platelet count, alcohol consumption, Alzheimer’s disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention

BackgroundAcute myeloid leukemia (AML) is a highly aggressive and pathogenic hematologic malignancy with consistently high mortality. Lysosomes are organelles involved in cell growth and metabolism that fuse to form specialized Auer rods in AML, and their role in AML has not been elucidated. This study aimed to identify AML subtypes centered on lysosome-related genes and to construct a prognostic model to guide individualized treatment of AML.MethodsGene expression data and clinical data from AML patients were downloaded from two high-throughput sequencing platforms. The 191 lysosomal signature genes were obtained from the database MsigDB. Lysosomal clusters were identified by unsupervised consensus clustering. The differences in molecular expression, biological processes, and the immune microenvironment among lysosomal clusters were subsequently analyzed. Based on the molecular expression differences between lysosomal clusters, lysosomal-related genes affecting AML prognosis were screened by univariate cox regression and multivariate cox regression analyses. Algorithms for LASSO regression analyses were employed to construct prognostic models. The risk factor distribution, KM survival curve, was applied to evaluate the survival distribution of the model. Time-dependent ROC curves, nomograms and calibration curves were used to evaluate the predictive performance of the prognostic models. TIDE scores and drug sensitivity analyses were used to explore the implication of the model for AML treatment.ResultsOur study identified two lysosomal clusters, cluster1 has longer survival time and stronger immune infiltration compared to cluster2. The differences in biological processes between the two lysosomal clusters are mainly manifested in the lysosomes, vesicles, immune cell function, and apoptosis. The prognostic model consisting of six prognosis-related genes was constructed. The prognostic model showed good predictive performance in all three data sets. Patients in the low-risk group survived significantly longer than those in the high-risk group and had higher immune infiltration and stronger response to immunotherapy. Patients in the high-risk group showed greater sensitivity to cytarabine, imatinib, and bortezomib, but lower sensitivity to ATRA compared to low -risk patients.ConclusionOur prognostic model based on lysosome-related genes can effectively predict the prognosis of AML patients and provide reference evidence for individualized immunotherapy and pharmacological chemotherapy for AML.

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion—a potential target for future immunotherapeutic interventions.

The p-type Te-free Cu3SbSe4 with famatinite structure is a potential candidate for thermoelectric materials due to the low cost and eco-friendly constituent elements. However, its strong bipolar effect and high lattice thermal conductivity (κlat) are the main challenges for its performance enhancement. Herein, we report a new strategy to enhance its figure of merit zT ∼0.86 at 673 K for Cu3Sb0.95Fe0.05Se2.8S1.2 via band structure tuning and hierarchical architecture. Firstly, S substituted Se atoms in lattice can widen the band gap to alleviate the bipolar effect. Secondly, Fe doping in Sb site significantly increases the density of states, thus increasing the carrier effective mass, and obtaining a remarkably high Seebeck coefficient of ∼560 μV/K at 300 K. Moreover, the induced hierarchical architecture defects resulting in a minimum κlat of ∼0.48 W·m−1·K−1 at 673 K. Consequently, the improved Seebeck coefficient combined with low thermal conductivity leads to an enhanced zT.

Adding high melting point nano-particles to the weld seam is an effective method to improve the thermal crack sensitivity and mechanical properties of aluminum alloy fusion welded joints, and a reasonable heat treatment process will further improve the mechanical properties of the welded joints. In this work, effects of heat treatment on the microstructure and mechanical properties of spray formed 7055 aluminum alloy TIG welded joints reinforced by ZrB2/Al3(Sc, Zr) particles were investigation. The results revealed that the precipitates in S1-SZ7 and S1-Z7 weld seams were η´ phase, and the precipitates in the S1-SZ7 weld seam were smaller, more abundant and dispersed than that in the S1-Z7 weld seam. As a result, the mechanical properties of the S1-SZ7 welded joint were better than those of the S1-Z7 welded joint. Fine grain strengthening, dispersion strengthening, and precipitation strengthening were the reasons for the improvement of mechanical properties of S1-SZ7 welded joints. With the extension of the secondary aging time, the η´ phases in the SZ7 weld seam transformed into η phase, and the precipitated phases gradually became coarse. The mechanical properties of S1-SZ7, S2-SZ7, and S3-SZ7 welded joints gradually decreased.

Adding nano ceramic particles to the weld seam is an effective way to improve the strength of the spray formed 7055 aluminum alloy welded joint. However, nano ceramic particles are prone to agglomeration, and the agglomerated nano ceramic particles in welded joint can cause stress concentration and brittle fracture of the specimen. In order to improve the aggregation of nano ZrB2 ceramic particles in the weld seam and further improve the mechanical properties of spray formed 7055 aluminum alloy TIG welded joint, Sc/ZrB2-7055 (SZ7) and ZrB2-7055 (Z7) welded joints were prepared in this study. Compared to the Z7 weld seam with coarse grains and severe aggregation of ZrB2 particles, the SZ7 weld seam has fine grains, and the distribution of ZrB2, Al3(Sc, Zr), and Sc modified ZrB2 particles in the weld seam was more uniform. The tensile strength and elongation of Z7 welded joints were 281 MPa and 2.0%, while the tensile strength and elongation of SZ7 welded joints were 320 MPa and 4.9%. The tensile strength and elongation values of SZ7 welded joints have increased by 13.8% and 145% respectively compared to Z7 welded joints. Sc elements formed a rich Sc layer on the surface of ZrB2 particles, which passivated the sharp corners of ZrB2 particles and increased the wettability between ZrB2 particles and Al liquid, resulting in uniform distribution of ZrB2 particles in the weld seams. Fine grain strengthening, dispersion strengthening, and dislocation strengthening are the main reasons for improving the mechanical properties of SZ7 welded joints.

To align with the global trend of integrating synchrotron light source (SLS) and free electron laser (FEL) facilities on one site, in line with examples such as SPring-8 and SACLA in Japan and ELETTRA and FERMI in Italy, we actively explore FEL options leveraging the ultralow-emittance electron beam of the NSLS-II upgrade. These options show promising potential for synergy with storage ring (SR) operations, thereby significantly enhancing our facility’s capabilities. Echo-enabled harmonic generation (EEHG) is well-suited to SR-based FELs, and has already been demonstrated with the capability of generating extremely narrow bandwidth as well as high brightness, realized using diffraction-limited short pulses in transverse planes and Fourier transform-limited bandwidth in the soft X-ray spectrum. However, regarding a conventional EEHG scheme, the combination of the shortest seed laser wavelength (256 nm) and highest harmonic (200) sets the short wavelength limit to λ = 1.28 nm. To further extend the short wavelength limit down to the tender and hard X-ray region, a vital option is to shorten the seed laser wavelength. Thanks to recent advances in high harmonic generation (HHG), packing 109 photons at one harmonic within a few-femtosecond pulse could turn such a novel HHG source into an ideal seeding for EEHG. Thus, compared to the cascaded EEHG, the HHG seeding option could not only lower the cost, but also free the SR space for accommodating more user beamlines. Moreover, to mitigate the SASE background noise on the sample and detector, we combine the HHG seeding EEHG with the crab cavity short pulse scheme for maximum benefit.

Abstract Background and aim Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. Methods A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan–Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. Results This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase

Abstract Background Light is a key regulatory factor for photosynthesis and metabolism of microalgae. The diatom Phaeodactylum tricornutum is capable of exhibiting metabolic flexibility in response to light fluctuations. However, the metabolic switching and underlying molecular mechanisms upon illumination transitions remain poorly understood for this industrially relevant marine alga. To address these, the physiochemical and molecular responses of P. tricornutum upon high light (HL) and recovery (HLR) were probed. Results Upon HL, P. tricornutum exhibited quick responses, including decreases in cell division, major light harvesting pigments (e.g., chlorophyll a, β-carotene, and fucoxanthin), chloroplastidic membrane lipids (e.g., monogalactosyldiacylglycerol, digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol), and long-chain polyunsaturated fatty acids (e.g., C20:5), as well as increases in carbohydrates and neutral lipids particularly triacylglycerol. During HLR stage when the stress was removed, these physiochemical phenotypes were generally recovered, indicative of a rapid and reversible changes of P. tricornutum to cope with illumination transitions for survival and growth. Through the integrated analysis with time-resolved transcriptomics, we revealed the transcriptional control of photosynthesis and carbon metabolism in P. tricornutum responding to HL, which could be reversed more or less during the HLR stage. Furthermore, we highlighted key enzymes involved in carotenoid biosynthesis and lipid metabolism of P. tricornutum and identified monooxygenases putatively responsible for catalyzing the ketolation step towards fucoxanthin synthesis from neoxanthin. Conclusions The detailed profiling of physiochemical and transcriptional responses of P. tricornutum to HL-HLR treatments advances our understanding on the adaption of the alga to illumination transitions and provides new insights into engineering of the alga for improved production of value-added carotenoids and lipids.

The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387–0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.

Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p

AbstractObjectives To evaluate the clinical utility of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in foetuses with oligohydramnios.Methods In this retrospective study, 126 fetuses with oligohydramnios at our centre from 2018 to 2021 were reviewed. The results of CMA and WES were analysed.Results One hundred and twenty-four cases underwent CMA and 32 cases underwent WES. The detection rate of pathogenic/likely pathogenic (P/LP) copy number variant (CNV) by CMA was 1.6% (2/124). WES revealed P/LP variants in 21.8% (7/32) of the foetuses. Six (85.7%, 6/7) foetuses showed an autosomal recessive inheritance pattern. Three (42.9%, 3/7) variants were involved in the renin–angiotensin–aldosterone system (RAAS), which are the known genetic causes of autosomal recessive renal tubular dysgenesis (ARRTD).Conclusion CMA has low diagnostic utility for oligohydramnios, while WES offers obvious advantages in improving the detection rate. WES should be recommended for fetuses with oligohydramnios.

Abstract Background A multitude of studies have highlighted that copy number variants (CNVs) are associated with neurodevelopmental disorders (NDDs) characterized by a wide range of clinical characteristics. Benefiting from CNV calling from WES data, WES has emerged as a more powerful and cost-effective molecular diagnostic tool, which has been widely used for the diagnosis of genetic diseases, especially NDDs. To our knowledge, isolated deletions on chromosome 1p13.2 are rare. To date, only a few patients were reported with 1p13.2 deletions and most of them were sporadic. Besides, the correlation between 1p13.2 deletions and NDDs remained unclear. Case presentation Here, we first reported five members in a three-generation Chinese family who presented with NDDs and carried a novel 1.41 Mb heterozygous 1p13.2 deletion with precise breakpoints. The diagnostic deletion contained 12 protein-coding genes and was observed to segregate with NDDs among the members of our reported family. Whether those genes contribute to the patient’s phenotypes is still inconclusive. Conclusions We hypothesized that the NDD phenotype of our patients was caused by the diagnostic 1p13.2 deletion. However, further in-depth functional experiments are still needed to establish a 1p13.2 deletion-NDDs relationship. Our study might supplement the spectrum of 1p13.2 deletion-NDDs.

Abstract Objectives To investigate the prognostic value of computed tomography fractional flow reserve (CT-FFR) in patients with diabetes and to establish a risk stratification model for major adverse cardiac event (MACE). Methods Diabetic patients with intermediate pre-test probability of coronary artery disease were prospectively enrolled. All patients were referred for coronary computed tomography angiography and followed up for at least 2 years. In the training cohort comprising of 957 patients, two models were developed: model1 with the inclusion of clinical and conventional imaging parameters, model2 incorporating the above parameters + CT-FFR. An internal validation cohort comprising 411 patients and an independent external test cohort of 429 patients were used to validate the proposed models. Results 1797 patients (mean age: 61.0 ± 7.0 years, 1031 males) were finally included in the present study. MACE occurred in 7.18% (129/1797) of the current cohort during follow- up. Multivariate Cox regression analysis revealed that CT-FFR ≤ 0.80 (hazard ratio [HR] = 4.534, p

Abstract Background Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. Methods This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. Results A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt–Jakob disease (13.4%), Alzheimer’s disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P

This study centered around the practical problem that there is no machine available for deep planting with large holes in hilly and mountainous areas of China. According to the principle of spiral lifting, a conical, double-spiral hole-forming machine was innovatively designed. The structural design and parameter calculation were completed. By discrete-element-method (DEM) simulation, the optimal lead and rotation speed of the hole former were obtained, and the hole-forming mechanisms of soil cutting, soil lifting, soil discharging, soil extruding, and soil returning were further revealed. The field test results indicated that the prototype had the advantages of convenient operation and good performance, and the formed holes met the agronomic requirements, with a qualification rate of 88.5%. In addition, it was found that the soil moisture content has a great influence on the formation of holes. Under the condition of low moisture content, the residence time at the bottom of a hole should be appropriately increased to improve the qualification rate of the holes formed. Our research results provided theoretical guidance and technical support for the design, optimization, popularization, and application of a hole-forming machine for deep planting with large holes (DPLH).

Harmful substances in consumer goods pose serious hazards to human health and the environment. However, due to the vast variety of consumer goods and the complexity of their substrates, it is difficult to simultaneously detect multiple harmful substances in different materials. This paper presents a method for the simultaneous determination of 41 harmful substances comprising 17 phthalates (PAEs), 8 organophosphate flame retardants (OPFRs), and 16 polycyclic aromatic hydrocarbons (PAHs) in five types of products using the matrix-matching calibration strategy. The method employs an efficient ultrasonic extraction procedure using a mixture of dichloromethane and methylbenzene, followed by dissolution–precipitation and analysis through gas chromatography–mass spectrometry. Compared with previous experiments, we established a universal pretreatment method suitable for multi-matrix materials to simultaneously determine multiple harmful substances. To evaluate the effects of the matrix on the experimental results, we compared neat standard solutions and matrix-matching standard solutions. The results demonstrated that all compounds were successfully separated within 30 min with excellent separation efficiency. Additionally, the linear relationships of all analytes showed strong correlation coefficients (R2) of at least 0.995, ranging from 0.02 mg/L to 20 mg/L. The average recoveries of the target compounds (spiked at three concentration levels) were between 73.6 and 124.1%, with a relative standard deviation (n = 6) varying from 1.2% to 9.9%. Finally, we tested 40 different materials from consumer products and detected 16 harmful substances in 31 samples. Overall, this method is simple and accurate, and it can be used to simultaneously determine multiple types of hazardous substances in multi-matrix materials by minimizing matrix effects, making it an invaluable tool for ensuring product safety and protecting public health.

BackgroundOverexpression of the cytokine receptor-like factor 2 (CRLF2) gene is the most common feature in the Philadelphia chromosome (Ph)-like subtype of B-cell acute lymphoblastic leukemia (B-ALL). However, the predictive value of CRLF2 overexpression for the prognosis of pediatric B-ALL patients remain controversial. The molecular mechanisms that upregulate CRLF2 expression level in patients has not been fully elucidated.MethodsIn this study, the prognostic impact of CRLF2 expression level on molecular types of B-ALL in pediatric patients from Zhujiang Hospital (n = 111) was retrospectively analyzed. Youden index analysis was used to categorize CRLF2 expression into 3 groups, and these categories more precisely described the differences in the prognosis of patients with varying expression levels of CRLF2 in both the Zhujiang Hospital cohort and the TARGET cohort.ResultsWe used the Zhujiang Hospital cohort as a discovery cohort to determine the cutoff value of CRLF2 expression. CRLF2-high patients accounted for approximately 6%. In addition, the percentage of bone marrow blast cells and initial white blood cell count in CRLF2-high patients were higher than those in CRLF2-low patients, and MRD turned negative slower. The results were validated in the TARGET cohort and indicated that CRLF2 overexpression could be subdivided by CRLF2 expression levels into 2 categories: CRLF2-high with a poor survival and CRLF2-medium with a good OS and EFS. Such heterogeneity was attributed to the different molecular mechanisms leading to CLRF2 upregulation, where the CRLF2 overexpression level was high in Ph-like B-ALL and medium in high hyperdiploid B-ALL.ConclusionThis study highlights the importance of the molecular mechanisms of the upregulation of CRLF2 expression in predicting the prognosis of pediatric B-ALL patients.

Abstract Objective To identify the key drugs of Yangyin Fuzheng Jiedu prescription (YFJP) and investigate their therapeutic effects against hepatocellular carcinoma (HCC) and the potential mechanism using network pharmacology. Methods The H22 tumor‐bearing mouse model was established. Thirty male BALB/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14 days. The mice were weighed every 2 days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor‐infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. The proportion of CD8+ T cells and the expression of programmed cell death protein 1 (PD‐1), T cell immunoglobulin domain and mucin domain‐3 (Tim‐3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex® MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC‐related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component‐target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene–gene inner and component‐target‐pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor‐bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking. Results Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor‐bearing mice. FZP increased the immune organ index and the levels of CD8+ and CD3+ T cells in the spleen and peripheral blood of H22 tumor‐bearing mice. FZP also reduced the expression of PD‐1, TIGIT, and TIM3 in CD8+ T cells and the production of IL‐10, IL‐4, IL‐6, and IL‐1β. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC‐related signaling pathways, including the PIK3‐Akt signaling pathway, PD‐L1 expression, and PD‐1 checkpoint pathway in cancer. GO enrichment analysis indicated that FZP positively regulated the molecular functions of transferases and kinases on the cell surface through membrane raft, membrane microarea, and other cell components to inhibit cell death and programmed cell death. Conclusion FZP was found to be the key disassembled prescription of YFJP that exerted antitumor and immunoregulatory effects against HCC. FZP alleviated T cell exhaustion and improved the immunosuppressive microenvironment via HCC‐related targets, pathways, and biological processes.

In this study, fine position samples of heat affected zone under single and secondary thermal cycles were simulated by heat treatment method. The influence of secondary thermal cycle on softening behavior and mechanism of heat affected zone in TIG-welded spray formed 7055 aluminum alloy were studied. The results showed that the mechanical properties of the solid solution zone decreased after the second thermal cycle. The hardness of the solid solution zone decreased from 180HV to 103HV and the tensile strength decreased from 570 MPa to 346 MPa after the second thermal cycle. The main reasons for the reduction of mechanical properties in the solid solution zone after the second thermal cycle were the weakening of the solid solution strengthening effect and the occurrence of over-aging. After the second thermal cycle in the over-aging zone, the mechanical properties decreased and then increased with the increase of the thermal cycle temperature. The lowest hardness value in the over-aging zone after the second thermal cycle decreased from 124HV to 103HV, and the tensile strength decreased from 410 MPa to 284 MPa. The main reason for the decrease of mechanical properties in the overaging zone after the secondary thermal cycle was the intensification of overaging caused by the coarsening of η phase. Overall, the width of the heat affected zone increased after the secondary thermal cycle, and the most seriously softened area extended toward the fusion line.

In this study, the Al–KBF4–K2TiF6–Y in situ reaction system was used to prepare rare earth (RE) element Y-modified TiB2 ceramic particles reinforced 7055 aluminum alloy welding consumables for inert gas shielded welding of spray-formed 7055 aluminum alloy. Compared with 0 Y- weld metal (WM), the grain size of the 0.1 Y-WM was refined from 30 μm to 25 μm. In the as-welded state, the tensile strength and elongation of 0 Y-7xxx and 0.1 Y-7xxx joints were 295 ± 6 MPa and 4.92 ± 0.24%, 327 ± 5 MPa and 6.45 ± 0.25%, respectively. The tensile strength and elongation of 0 Y-7xxx and 0.1 Y-7xxx joints after T6 heat treatment were 521 ± 5 MPa and 3.47 ± 0.24%, 557 ± 6 MPa and 4.84 ± 0.25%, respectively. The elongation of the 0.1Y-7xxx joint is 55.47% higher than that of the 0 Y-7xxx joint. The introduction of rare earth elements Y can improve the wettability of TiB2 particles and the substrate so that TiB2 particles are uniformly dispersed, and at the same time make TiB2 particles edge blunting, thereby improving the mechanical properties of welded joints.

In light of the escalating global energy crisis, microalgae have emerged as highly promising producers of biofuel and high-value products. Among these microalgae, Nannochloropsis has received significant attention due to its capacity to generate not only triacylglycerol (TAG) but also eicosapentaenoic acid (EPA) and valuable carotenoids. Recent advancements in genetic tools and the field of synthetic biology have revolutionized Nannochloropsis into a powerful biofactory. This comprehensive review provides an initial overview of the current state of cultivation and utilization of the Nannochloropsis genus. Subsequently, our review examines the metabolic pathways governing lipids and carotenoids, emphasizing strategies to enhance oil production and optimize carbon flux redirection toward target products. Additionally, we summarize the utilization of advanced genetic manipulation techniques in Nannochloropsis. Together, the insights presented in this review highlight the immense potential of Nannochloropsis as a valuable model for biofuels and synthetic biology. By effectively integrating genetic tools and metabolic engineering, the realization of this potential becomes increasingly feasible.

Solid lubricating films have great advantages in extreme operating conditions. In this research, silver (Ag) was doped into the ZrMoN composite film to develop a composite polyphase structure with enhanced mechanical and tribological properties. A series of ZrMoN–Ag composite films with different Ag content were prepared. The results show that the composition phases of the composite films are fcc-Mo2N、fcc-ZrN, and nano-crystalline fcc-Ag was dispersed in the films. The ZrMoN–Ag composite films exhibited excellent mechanical properties with a hardness of 27.6 GPa and elastic modulus of 286.8 GPa. In addition, the ZrMoN–Ag composite film with Ag content of 11.88 at.% possessed the advantage of low friction coefficient in a wide temperature range, attributing mainly to the synergetic effect of Ag phase and friction oxidation products. This work provides a promising solution for designing solid self-lubrication composite in wide temperature domain.

Due to the brittle weld joints and worsening hot cracking tendency of spray-formed (SF) 7055 aluminum alloy, they are regarded as un-weldable. In this study, TiB2–Al3Ti/7055 (MA) aluminum matrix composites manufactured by the master alloy method were used to connect SF 7055 aluminum alloy. In the as-weld state, ceramic particles refine α-Al grains in weld metal (WM) and reduce the hot cracking tendency of weld joints. The tensile properties of weld joints increased from 240 ± 5 MPa, 1.4 ± 0.24% (7055) to 284 ± 5 MPa, 4.0 ± 0.35% (MA). In the heat treatment states (T6, T76, and RRA), the mechanical properties and corrosion resistance of MA-WM are superior to 7055-WM. The tensile strength of MA-T6 (485 ± 20 MPa, 3.10 ± 0.23%) is the best of the three heat treatment states, while the corrosion resistance of MA-T76 is the best. MA-RRA gains mechanical properties similar to MA-T6 and corrosion resistance close to MA-T76.

In this investigation, fine micro-zone specimens in the heat-affected zone (HAZ) of TIG welded spray formed 7055 aluminum alloy were obtained by heat treatment method. The softening behavior and mechanism of HAZ of this alloy under single pass TIG welding were investigated. Severe non-uniformities of microstructures and mechanical properties were found, according to which the HAZ was divided into the solid solution zone and the over-aging zone. The most heavily softened area of HAZ occurred in the over-aging zone at the position corresponding to the peak thermal cycling temperature of 230–350 °C. The lowest microstructures value was 105 HV, the lowest tensile strength was about 410 MPa. The elongation was slightly higher than that of the base material. The main causes of softening in the over-aging zone were the dissolution of the coherent precipitate η′ and the growth and coarsening of the non-coherent precipitate η.Thermal cycle temperature in the solid solution zone was about 350–536 °C. Mechanical properties in this zone were higher than those of the over-aging zone. After natural aging, mechanical properties recovered to more than 90% of the base material. Microhardness reached 180 HV and tensile strength reached 570 MPa when the thermal cycle temperature was 450 °C. At the same time, the elongation in the solid solution zone was higher than that of the base material. The high mechanical properties were the results of the combined action of the increased ratio of large angle grain boundaries, the increased solid solubility and the formation of coherent GPI zone.

The coronavirus disease 2019 (COVID-19) pandemic has clearly had a great influence on the lifestyles of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social-isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist COVID-19, ultimately causing severe prognoses. Moreover, as the epidemic progressed, multiple studies emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19. In this study, we selected research from 1 December 2019 to 9 August 2023 that focused on COVID-19-infected diabetic patients to investigate the impact of type 2 diabetes on the immune functions, inflammation factor levels, lung injuries, and mental disorders of such patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. Additionally, the effects of high-intensity, moderate-intensity, and low-intensity exercises on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of the effects of such exercise were considered. We concluded that elderly diabetic patients with COVID-19 should perform low-intensity exercises to facilitate their recoveries. This study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.

Cu3SbSe4 is a potential p-type thermoelectric material, distinguished by its earth-abundant, inexpensive, innocuous, and environmentally friendly components. Nonetheless, the thermoelectric performance is poor and remains subpar. Herein, the electrical and thermal transport properties of Cu3SbSe4 were synergistically optimized by S alloying. Firstly, S alloying widened the band gap, effectively alleviating the bipolar effect. Additionally, the substitution of S in the lattice significantly increased the carrier effective mass, leading to a large Seebeck coefficient of ~730 μVK−1. Moreover, S alloying yielded point defect and Umklapp scattering to significantly depress the lattice thermal conductivity, and thus brought about an ultralow κlat ~0.50 Wm−1K−1 at 673 K in the solid solution. Consequently, multiple effects induced by S alloying enhanced the thermoelectric performance of the Cu3SbSe4-Cu3SbS4 solid solution, resulting in a maximum ZT value of ~0.72 at 673 K for the Cu3SbSe2.8S1.2 sample, which was ~44% higher than that of pristine Cu3SbSe4. This work offers direction on improving the comprehensive TE in solid solutions via elemental alloying.

Abstract Background Pediatric leukemia is the most prevalent childhood cancer in China and incurs heavy economic burden to patients without sufficient insurance protection. Although all Chinese children are obliged to enroll in the national insurance scheme, “Resident Basic Medical Insurance (RBMI)”, the protection may vary among patient subgroups. This study is designed to measure the disparities in economic burden for patients with leukemia under RBMI protection and explore the influencing factors. Methods The included patients were aged ≤ 15 and diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML, with/without transplantation). They all completed treatment course consecutively in Nanfang Hospital and Zhujiang Hospital from Jan.1, 2015, to Dec.30, 2019, in Guangzhou, China. Their inpatient treatment and insurance settlement data were drawn from the Hospital Information System (HIS) and Insurance Settlement System (ISS). A total of 765 consecutive patients and 14,477 inpatient medical records were included and analyzed. Their insurance status (6 subtypes), economic burden [total cost, out-of-pocket cost (OOP), reimbursement, reimbursement rate (RR)], and cost structures (operation/procedure, blood products, drug, simple treatment) were calculated respectively. Non-normally distributed costs were reported as the median and interquartile range (IQR). Wilcoxon test was used for univariate tests and generalized linear model with log link was used to explore the influencing factors. Results The insured patients who were treated in the location of insurance with instant reimbursement reported the highest total cost and reimbursement, while those who seek medical care cross-province with no instant reimbursement reported the lowest total cost and highest OOP payment. In terms of annual change, the total cost of children with leukemia decreased from 2015–2019 with stably increasing reimbursement rate. Blood products and drugs were the major components of total cost, but they decreased annually. Patients who received transplantation and treated across provinces were with a higher economic burden. Conclusion The economic burden for children with leukemia decreased overtime under the protection of RBMI, but disparities exist among subtypes. The payer-provider contract on instant reimbursement and drug cost control are effective measures for insurance administrators to curb the economic burdens of pediatric leukemia treatment.

Abstract Background The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. Methods A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. Results After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p

Background: Prenatal diagnosis of fetal short long bones (SLBs) was reported to be associated with skeletal dysplasias, chromosomal abnormalities, and genetic syndromes. This study aims to identify the genetic causes for fetal short long bones, and retrospectively evaluate the additional diagnostic yield of exome sequencing (ES) for short long bones following the use of conventional genetic testing.Methods: A cohort of ninety-four fetuses with sonographically identified short long bones was analyzed by trio-exome sequencing between January 2016 and June 2021. Fetuses with abnormal results of karyotype or chromosomal microarray analysis were excluded. Variants were interpreted based on ACMG/AMP guidelines. All diagnostic de novo variants were validated by Sanger sequencing.Results: Of the 94 fetuses, 38 (40.4%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in sixteen genes with 38 variants. Five fetuses (5.3%) had variant(s) of uncertain significance. Thirty-five cases (37.2%) were diagnosed as genetic skeletal dysplasias including 14 different diseases that were classified into 10 groups according to the Nosology and Classification of Genetic Skeletal Disorders. The most common disease in the cohort was achondroplasia (28.9%), followed by osteogenesis imperfecta (18.4%), thanatophoric dysplasia (10.5%), chondrogenesis (7.9%), and 3-M syndrome (5.3%). The diagnostic yield in fetuses with isolated short long bones was lower than the fetuses with non-isolated short long bones, but not reached statistical significance (27.3% vs. 44.4%; p = 0.151). Whereas, the rate in the fetuses with other skeletal abnormalities was significantly higher than those with non-skeletal abnormalities (59.4% vs. 32.5%, p = 0.023), and the diagnostic rate was significantly higher in femur length (FL) below -4SDs group compared with FL 2-4SDs below GA group (72.5% vs. 16.7%; p < 0.001). A long-term follow-up showed that outcomes for fetuses with FL 2-4SDs below GA were significantly better than those with FL below -4SDs. Additionally, fourteen (36.8%) novel short long bones-related variants were identified in the present study.Conclusion: The findings suggest that in fetuses with short long bones routine genetic tests failed to determine the underlying causes, exome sequencing could add clinically relevant information that could assist the clinical management of pregnancies. Novel pathogenic variants identified may broaden the mutation spectrum for the disorders and contributes to clinical consultation and subsequent pregnancy examination.

Owing to the notorious hot-crack susceptibility and severe softening fusion-weld joints of Al–Zn–Mg–Cu alloys, they are generally considered unweldable. In this study, TiC/7xxx (TC) and TiC–TiB2/7xxx (BC) aluminum matrix composites, fabricated by in-situ mixed-salt reaction, were used as filler rods of spray formed 7055 alloys to modify the microstructure and mechanical properties of TIG weld joints. Compared with 7055-weld metal (WM), the grain sizes of TC-WM and BC-WM were refined from 100 μm to 24 μm and 26 μm, respectively. The precipitation of eutectic phases in WM was reduced by ceramic particles, which decreased the hot-crack susceptibility of joints. In the as-welded state, the ultimate tensile strength of TC and BC joints increased from 240 ± 5 MPa to 274 ± 5 MPa and 300 ± 5 MPa, respectively. The addition of ceramic particles also improved the impact toughness and hardness of weld joints. Grain refinement, load-bearing strengthening, coefficients of thermal expansion mismatch strengthening, and Zener pinning strengthening are the dominant strengthening mechanisms of weld joints with ceramic particles.

Abstract Background The green microalga Chromochloris zofingiensis is capable of producing high levels of triacylglycerol rich in C18 unsaturated fatty acids (UFAs). FA desaturation degree is regulated by FA desaturases (FADs). Nevertheless, it remains largely unknown regarding what FADs are involved in FA desaturations and how these FADs collaborate to contribute to the high abundance of C18 UFAs in triacylglycerol in C. zofingiensis. Results To address these issues, we firstly determined the transcription start sites of 11 putative membrane-bound FAD-coding genes (CzFADs) and updated their gene models. Functional validation of these CzFADs in yeast and cyanobacterial cells revealed that seven are bona fide FAD enzymes with distinct substrates. Combining the validated functions and predicted subcellular compartments of CzFADs and the FA profiles of C. zofingiensis, the FA desaturation pathways in this alga were reconstructed. Furthermore, a multifaceted lipidomic analysis by systematically integrating thin-layer chromatography, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry techniques was conducted, unraveling profiles of polar membrane lipids in C. zofingiensis and major desaturation steps occurring in these lipids. By correlating transcriptional patterns of CzFAD genes and changes of lipids upon abiotic stress conditions, our results highlighted collaboration of CzFADs for C18 UFA synthesis and supported that both de novo FA synthesis and membrane lipid remodeling contributed C18 UFAs to triacylglycerol for storage. Conclusions Taken together, our study for the first time elucidated the pathways of C18 FA desaturations and comprehensive profiles of polar membrane lipids in C. zofingiensis and shed light on collaboration of CzFADs for the synthesis and enrichment of C18 UFAs in triacylglycerol.

Nowadays there is the need to avoid the excessive consumption of liquid lubricant oils, as they are harmful to the environment and hard to disposal. Self-lubricant films have been seen as the sustainable solution to achieve a long-term lubrication under high temperature-cycling conditions. In this manuscript, multilayer Mo2N-Ag/SiNx films with a fixed modulation ratio (thickness of Mo2N-Ag to SiNx) of 3:1, with changing modulation period (Λ, thickness of Mo2N-Ag and SiNx) from 8 to 200 nm were produced to achieve an effective balance between the lubricious phase diffusion control and the adequate formation of the low friction tribo-layers. Results showed that a dual-phase of fcc-Mo2N and fcc-Ag co-existed in Mo2N-Ag layers, while the SiNx layer exhibited an amorphous character. Both room temperature (RT) lubricant and wear-resistance properties of the films were improved by increasing Λ from 8 to 64 nm, while a further increase of Λ degraded the wear-resistance properties. The multilayer film at Λ = 64 nm exhibited an excellent RT-500 °C temperature-cycling tribological properties. Mechanical properties and the synergistic effect of both modulation layers were the cause for the improvement of the tribological properties.

The BCL-2 inhibitor venetoclax is currently approved for treatment of hematologic diseases and is widely used either as monotherapy or in combination strategies. It has produced promising results in the treatment of refractory or relapsed (R/R) and aged malignant hematologic diseases. However, with clinical use, resistance to venetoclax has emerged. We review the mechanism of reduced dependence on BCL-2 mediated by the upregulation of antiapoptotic proteins other than BCL-2, such as MCL-1 and BCL-XL, which is the primary mechanism of venetoclax resistance, and find that this mechanism is achieved through different pathways in different hematologic diseases. Additionally, this paper also summarizes the current investigations of the mechanisms of venetoclax resistance in terms of altered cellular metabolism, changes in the mitochondrial structure, altered or modified BCL-2 binding domains, and some other aspects; this article also reviews relevant strategies to address these resistance mechanisms.

Continuous cropping can lead to increased soil-borne diseases of sugar beet (Beta vulgaris L.), resulting in a reduction in its yield quality. However, our understanding of the influence of continuous cropping on sugar beet-associated microbial community is limited and their interactions remain unclear. Here, we described and analyzed microbial diversity (N = 30) from three sugar beet belowground compartments (bulk soil, rhizosphere soil, and beetroot) using 16S rRNA and ITS sequencing. The continuous cropping showed lower bacterial alpha diversity in three belowground compartments and higher fungal alpha diversity in roots compared to the non-continuous cropping. There were significant differences in fungal community composition between the two groups. Compared with non-continuous cropping, continuous cropping increased the relative abundance of potentially pathogenic fungi such as Tausonia, Gilbellulopsis, and Fusarium, but decreased the relative abundance of Olpidium. The fungal flora in the three compartments displayed different keystone taxa. Fungi were more closely related to environmental factors than bacteria. Overall, changes in microbial diversity and composition under continuous cropping were more pronounced in the fungal communities, and the results of the study could guide development strategies to mitigate continuous crop adversity.

Transition metal nitride (TMN) films with excellent hardness and lubricating performance are versatile low dimension materials, which are widely used in various fields including industries, transportation, aerospace, and so on. This paper introduces one film design strategy and provides a review of the mechanisms for strengthening and lubricating nitride films. The design strategy refers to two aspects which determine the structures, the performance, the components, and the chemical constitutions of nitride films The strengthening mechanisms of nitride films are then illuminated in detail, including the solid solution effect, the grain size effect, the secondary phase effect, the stress or stress field effect, the template effect, and the valence electron concentration effect. Five lubricating mechanisms are next summarized, including the easy-shear nature, the tribo-chemical reactions, the lubricious fluorides, the textured contact surface, and the synergistic effect. This paper aims to give a comprehensive introduction for understanding the mechanisms of strengthening and lubrication of nitride films for students and researchers, as well as to understand the current research progress in nitride films for exploring research gaps.

Abstract The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been considered to be crucial in tumor malignancy. Although CRNDE is highly expressed in acute myeloid leukemia (AML), its mechanism of action remains unknown. In this study, GEPIA and qRT-PCR were performed to confirm the expression of CRNDE in AML samples and cell lines, respectively. CRNDE shRNA vectors were transfected to explore the biological functions of CRNDE. The cell proliferation was assessed by the CCK8 assay, while apoptosis and cell cycle distribution were measured by flow cytometry and Western blotting. The results showed that CRNDE was overexpressed in both AML samples and cell lines. CRNDE silencing inhibited proliferation and increased apoptotic rate and cell cycle arrest of KG-1a cells. The luciferase reporter assay coupled with RIP assay revealed that CRNDE act as a ceRNA. Rescue assays demonstrated that the effects of CRNDE silencing could be reversed by miR-136-5p inhibitors. In conclusion, our results expound that the CRNDE/miR-136-5p/MCM5 axis modulates cell progression and provide a new regulatory network of CRNDE in KG-1a cells.

BackgroundRapid-onset dystonia parkinsonism (RDP) is a rare disease caused by ATP1A3 mutation with considerable clinical heterogeneity. Increased knowledge of RDP could be beneficial in its early diagnosis and treatment.ObjectiveThis study aimed to summarize the gene mutation spectrum of ATP1A3 associated with RDP, and to explore the correlation of ATP1A3 variants with RDP clinical phenotypes.MethodsIn this study, we reported two RDP patients from a family with a novel inherited ATP1A3 variant. Then, we reviewed and analyzed the available literature in English focused on ATP1A3-causative RDP. A total of 35 articles covering 15 families (59 patients) and 36 sporadic RDP cases were included in our analysis.ResultsThe variant A813V (2438C>T) in ATP1A3 found in our cases was a novel mutant. Delays in diagnosis were common, with a mean delay time of 14 years. ATP1A3 had distinct RDP-related mutation hotspots, which consisted of exon8, 14, 17, and 18, and the most frequently occurring variants were T613M and I578S. Approximately 74.5% of patients have specific triggers before disease onset, and 82.1% of RDPs have stable symptoms within 1 month. The incidence rates of dystonia and bradykinesia are 100 and 88.1%, respectively. The onset site varied and exhibited a rostrocaudal gradient distribution pattern in 45% of patients with RDP. Approximately 63.6% of patients had mild improvement after receiving comprehensive interventions, especially in gait disturbance amelioration.ConclusionIn patients with acute and unexplained dystonia or bradykinesia, gene screening on ATP1A3 should be timely performed. When a diagnosis has been made, treatments that may be effective are to be attempted. Our study would be helpful for the early diagnosis and treatment of ATP1T3-related RDP.

A dilated lateral ventricle is a relatively common finding on prenatal ultrasound, and the causes are complex. We aimed to explore the etiology of a fetus with a dilated lateral ventricle. Trio whole-exome sequencing was performed to detect causative variants. A de novo variant of TAOK1 (NM_020791.2: c.227A>G) was detected in the proband and evaluated for potential functional impacts using a variety of prediction tools. Droplet digital polymerase chain reaction was used to exclude the parental mosaicism and to verify the phasing of the de novo variant. Based on peripheral blood analysis, the parents did not exhibit mosaicism at this site, and the de novo variant was paternally derived. Here, we describe a fetus with a de novo likely pathogenic variant of TAOK1 who had a dilated lateral ventricle and a series of particular phenotypes. This case expands the clinical spectrum of TAOK1-associated disorders. We propose a method for solving genetic disorders in which the responsible genes have not yet gone through ClinGen curation, particularly for prenatal cases.

Hepatocellular carcinoma (HCC) is a severe cancer endangering human health. We constructed a novel glycometabolism-related risk score to predict prognosis and immunotherapy strategies in HCC patients. The HCC data sets were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, and the glycometabolism-related gene sets were obtained from the Molecular Signature Database. The least absolute contraction and selection operator (LASSO) regression model was used to construct a risk score based on glycometabolism-related genes. A simple visual nomogram model with clinical indicators was constructed and its effectiveness in calibration, accuracy, and clinical value was evaluated. We also explored the correlation between glycometabolism-related risk scores and molecular pathways, immune cells, and functions. Patients in the low-risk group responded better to anti-CTLA-4 immune checkpoint treatment and benefited from immune checkpoint inhibitor (ICI) therapy. The study found that glycometabolism-related risk score can effectively distinguish the prognosis, molecular and immune-related characteristics of HCC patients, and may provide a new strategy for individualized treatment.

In this study, atypical choroid plexus papilloma was treated with high-dose rapamycin for 17 days preoperatively in an infant. Rapamycin significantly reduced the blood supply to the tumor while reducing the tumor volume, and most of the tumor was resected successfully. However, the infant developed hyperglycemia related to the rapamycin dose, which was effectively controlled by adjusting the dose and applying insulin.

KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in KDSR that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient.

Abstract Background Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is widely applied in couples with single reciprocal translocation to increase the chance for a healthy live birth. However, limited knowledge is known on the data of PGT-SR when both parents have a reciprocal translocation. Here, we for the first time present a rare instance of PGT-SR for a non-consanguineous couple in which both parents carried an independent balanced reciprocal translocation and show how relevant genetic counseling data can be generated. Methods The precise translocation breakpoints were identified by whole genome low-coverage sequencing (WGLCS) and Sanger sequencing. Next-generation sequencing (NGS) combining with breakpoint-specific polymerase chain reaction (PCR) was used to define 24-chromosome and the carrier status of the euploid embryos. Results Surprisingly, 2 out of 3 day-5 blastocysts were found to be balanced for maternal reciprocal translocation while being normal for paternal translocation and thus transferable. The transferable embryo rate was significantly higher than that which would be expected theoretically. Transfer of one balanced embryo resulted in the birth of a healthy boy. Conclusion(s) Our data of PGT-SR together with a systematic review of the literature should help in providing couples carrying two different reciprocal translocations undergoing PGT-SR with more appropriate genetic counseling.

Anethum foeniculum is an important medicinal plant in traditional Chinese medicine. In this paper, we characterized and reported the chloroplast genome of Anethum foeniculum. Its sequence length is 153,618 bp, which contains a large single-copy (LSC) region of 86,651 bp, a small single-copy (SSC) region of 17,471 bp, and a pair of inverted repeats (IR) regions of 24,748 bp. The overall nucleotide composition of the chloroplast genome sequence is: A (30.8%), T (31.5%), C (19.2%), G (18.5%) and the total G + C content of 37.7%. The complete chloroplast genome sequence contains 130 genes, including 85 encoding genes, 37 transfer RNA genes and 8 ribosomal RNA genes. The phylogenetic analysis result of this study reveals that Anethum foeniculum is closely related to Anethum foeniculum (NC_029469) in the phylogenetic relationship.

ObjectiveT cell immunity plays an important role in anti-tumor effects and immunosuppression often leads to the development and relapse of cancer. This study aimed to investigate the effect of T cell numbers on the long-term prognosis of patients with hepatocellular carcinoma (HCC) and construct an artificial neural network (ANN) model to evaluate its prognostic value.MethodsWe enrolled 3,427 patients with HCC at Beijing Ditan Hospital, Capital Medical University, and randomly divided them into two groups of 1,861 and 809 patients as the training and validation sets, respectively. Cox regression analysis was used to screen for independent risk factors of survival in patients with HCC. These factors were used to build an ANN model using Python. Concordance index, calibration curve, and decision curve analysis were used to evaluate the model performance.ResultsThe 1-year, 3-year, 5-year, and 10-year cumulative overall survival (OS) rates were 66.9%, 45.7%, 34.9%, and 22.6%, respectively. Cox multivariate regression analysis showed that age, white blood cell count, creatinine, total bilirubin, γ-GGT, LDH, tumor size ≥ 5 cm, tumor number ≥ 2, portal vein tumor thrombus, and AFP ≥ 400 ng/ml were independent risk factors for long-term survival in HCC. Antiviral therapy, albumin, T cell, and CD8 T cell counts were independent protective factors. An ANN model was developed for long-term survival. The areas under the receiver operating characteristic (ROC) curve of 1-year, 3-year, and 5-year OS rates by ANNs were 0.838, 0.833, and 0.843, respectively, which were higher than those of the Barcelona Clinic Liver Cancer (BCLC), tumor node metastasis (TNM), Okuda, Chinese University Prognostic Index (CUPI), Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), and albumin–bilirubin (ALBI) models (P < 0.0001). According to the ANN model scores, all patients were divided into high-, middle-, and low-risk groups. Compared with low-risk patients, the hazard ratios of 5-year OS of the high-risk group were 8.11 (95% CI: 7.0-9.4) and 6.13 (95% CI: 4.28-8.79) (P

Introduction: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). Methods: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. Results: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor–lymph node–metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. Conclusions: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.