Mapping transcriptomic vector fields of single cells.

Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.

Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Fe and Cu Intercalations Enhance SERS of MoO3 through Different Mechanistic Pathways.

Surface Enhanced Raman spectroscopy (SERS) is a molecular-specific analytical technique with various applications. Although electromagnetic (EM) and chemical (CM) mechanisms have been proposed to be the main origins of SERS, exploring highly sensitive SERS substrates with well-defined mechanistic pathways remains challenging. Since surface and electronic structures of substrates were crucial for SERS activity, zero-valent transition metals (Fe and Cu) were intercalated into MoO3 to modulate its surface and electronic structures, leading to unexceptional high enhancement factors (1.0×108 and 1.1×1010 for Fe-MoO3 and Cu-MoO3 , respectively) with decent reproducibility and stability. Interestingly, different mechanistic pathways (CM and EM) were proposed for Fe-MoO3 and Cu-MoO3 according to mechanistic investigations. The different mechanisms of Fe-MoO3 and Cu-MoO3 were rationalized by the electronic structures of the intercalated Fe(0) and Cu(0), which modulates the surface and electronic structures of Fe-MoO3 and Cu-MoO3 to differentiate their SERS mechanisms.

Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis.

BACKGROUND: Despite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening. METHOD: A comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092. RESULTS: From an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity. CONCLUSIONS: Among the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report.

More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.

Prediction of mass spectrometry ionization efficiency based on COSMO-RS and machine learning algorithms.

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards.

Exosomal miR-93 derived from hepatocellular carcinoma cell promotes the sorafenib resistance of hepatocellular carcinoma through PTEN/PI3K/Akt pathway.

Exosomal microRNAs (miRNAs) derived from cancer cell is an important regulatory molecule that mediates the formation of tumor drug resistance, but function and mechanisms of exosomal miRNA in sorafenib resistance of hepatocellular carcinoma (HCC) have not been studied. We detected the level and prognosis of miR-93 in HCC by using TCGA HCC database. For confirming the extracted exosome, transmission electron microscopy was used. Cy3-labeled miR-93 and quantitative reverse transcription-polymerase chain reaction were used to prove that exosomal miR-93 derived from HCC cell can be transferred to sensitive HCC cells. CCK8, EdU, and flow cytometer assay were used to confirm the function of exosomal miR-93 in sorafenib resistance of HCC. Bioinformatics software and luciferase reporter assay was used to confirm the direct targeting relationship between PTEN and miR-93. Western blot was used to validate downstream pathways. We found that miR-93 is overexpressed and a prognostic risk factor for the HCC patients. miR-93 was overexpressed in sorafenib resistant HCC cells compared with sensitive cells, and miR-93 contributed to sorafenib resistance of HCC cells through targeting PTEN. miR-93 was enriched in exosomes that secreted from sorafenib resistant cells, and these exosomal miR-93 promote the spread of sorafenib resistant through targeting PTEN to reactivate PI3K/AKT pathway. Therefore, miR-93 can act as a potential therapeutic target for advanced patients with acquired sorafenib resistance.

NiCoP cocatalyst modified g-C3N4 as ohmic junction photocatalyst for efficient degradation of tetracycline under visible light.

Increasing the electron-hole recombination rate in g-C3N4 can effectively improve its photocatalytic performance. In this work, NiCoP/g-C3N4 (NCP/PCN) composites with ohmic junction were formed by embedding granular NiCoP in irregularly porous g-C3N4. There was almost no barrier between the metal and the semiconductor in ohmic junction, which made it easier for electrons to slip from PCN to NCP along the curved energy band, and NCP acted as an electron collector to rapidly capture the slipping electrons. In addition, porous g-C3N4 prepared by supramolecular self-assembly could provide a shorter diffusion path for electrons. Thus, the electron-hole was effectively separated and the photocatalytic performance was improved. The band electronic structure and existence of ohmic junction in 7-NCP/PCN composite were demonstrated by XPS, ESR and DFT calculation. Finally, a reasonable photocatalytic degradation mechanism and possible tetracycline degradation path were proposed. This work has significant potential for providing an effective method for the design of non-precious metal photocatalysts.

Cancer progression and tumor hypercoagulability: a platelet perspective.

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.

Quality assessment of paediatric randomized controlled trials published in China from 1999 to 2022: a cross-sectional study.

BACKGROUND: Randomized controlled trials (RCTs) are usually the basis of evidence-based medicine, but whether the results of RCTs can be correctly translated into clinical practice depends on the quality of the literature reported. In this study, we evaluated the general characteristics and quality of paediatric RCTs published in China to provide evidence for the reporting of paediatric RCTs and their application in clinical practice. METHODS: We conducted a cross-sectional observational study of paediatric RCTs published in paediatric journals in China between January 1, 1999, and December 30, 2022. All RCTs that included children (younger than 18 years old) were retrieved, and the general characteristics of the RCTs were extracted and analysed. The quality of the RCTs was assessed by the Cochrane quality assessment protocol. RESULTS: After screening 20 available paediatric journals, 3545 RCTs were included for analysis. The average annual growth rate of the number of published paediatric RCTs from 1999 to 2022 was 7.8% (P = 0.005, R2 = 0.311). Most of the studies were carried out in East China [1148 (32.4%]; the centres of the RCTs were mainly single-centre [3453 (97.4%], and the interventions were mainly medication [2442 (68.9%)]. Comparing RCTs published in 2017-2022 with RCTs published in 1999-2004, the quality of RCTs significantly improved in terms of random sequence generation, allocation concealment, blinding participants and personnel, incomplete outcome data and selective outcome reporting. RCTs published in multiple centres from the Chinese Science Citation Database were identified, and the approval of the ethics committee was of better quality for all the analysed risk of bias items. CONCLUSION: The number and quality of paediatric RCTs reported in China have improved in recent years, but the overall quality was relatively low. Special attention should be given to allocation concealment and blinding outcome assessment, and dropouts, adverse effects and sample size calculations should be reported. Promoting government policies, strengthening the standardization of journal publishing and advancing the registration of clinical trials are feasible measures.

The interaction of Pu.1 and cMyb in zebrafish neutrophil development.

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited. PU.1 and cMYB participate in multiple stages of neutrophil development, and their abnormalities are often associated with hematologic disorders. However, the regulatory relationship between these factors in vivo and their mode of interaction remain unclear. In this study, zebrafish models with cMyb overexpression (cmybhyper) and Pu.1 deficiency (pu.1G242D/G242D) were utilized to systematically investigate the interaction between Pu.1 and cMyb during granulopoiesis through whole-mount in situ hybridization, qRT-PCR, fluorescence reporting systems, and rescue experiments. The results showed a significant increase in cmyb expression in neutrophils of the pu.1G242D/G242D mutant, while there was no apparent change in pu.1 expression in cmybhyper. Further experiments involving injection of morpholino (MO) to decrease cmyb expression in pu.1G242D/G242D mutants, followed by SB and BrdU staining to assess neutrophil quantity and proliferation, revealed that reducing cmyb expression could rescue the abnormal proliferation phenotype of neutrophils in the pu.1G242D/G242D mutant. These findings suggest that Pu.1 negatively regulates the expression of cMyb during neutrophil development. Finally, through the construction of multi-site mutation plasmids and a fluorescent reporter system, confirmed that Pu.1 directly binds to the +72 bp site in the cmyb promoter, exerting negative regulation on its expression. In conclusion, this study delineates that Pu.1 participates in neutrophil development by regulating cmyb expression. This provides new insights into the regulatory relationship between these two factors and their roles in diseases.

Pharmacokinetics and tissue distribution of vigabatrin enantiomers in rats.

Purpose: To investigate the pharmacokinetics and tissue distribution of VGB racemate and its single enantiomers, and explore the potential of clinic development for single enantiomer S-VGB. Methods: In the pharmacokinetics study, male Sprague-Dawley rats were gavaged with VGB racemate or its single enantiomers dosing 50, 100 or 200 mg/kg, and the blood samples were collected during 12 h at regular intervals. In the experiment of tissue distribution, VGB and its single enantiomers were administered intravenously dosing 200 mg/kg, and the tissues including heart, liver, spleen, lung and kidney, eyes, hippocampus, and prefrontal cortex were separated at different times. The concentrations of R-VGB and S-VGB in the plasma and tissues were measured using HPLC. Results: Both S-VGB and R-VGB could be detected in the plasma of rats administered with VGB racemate, reaching Cmax at approximately 0.5 h with t1/2 2-3 h. There was no significant pharmacokinetic difference between the two enantiomers when VGB racemate was given 200 mg/kg and 100 mg/kg. However, when given at the dose of 50 mg/kg, S-VGB presented a shorter t1/2 and a higher Cl/F than R-VGB, indicating a faster metabolism of S-VGB. Furthermore, when single enantiomer was administered respectively, S-VGB presented a slower metabolism than R-VGB, as indicated by a longer t1/2 and MRT but a lower Cmax. Moreover, compared with the VGB racemate, the single enantiomers S-VGB and R-VGB had shorter t1/2 and MRT, higher Cmax and AUC/D, and lower Vz/F and Cl/F, indicating the stronger oral absorption and faster metabolism of single enantiomer. In addition, regardless of VGB racemate administration or single enantiomer administration, S-VGB and R-VGB had similar characteristics in tissue distribution, and the content of S-VGB in hippocampus, prefrontal cortex and liver was much higher than that of R-VGB. Conclusions: Although there is no transformation between S-VGB and R-VGB in vivo, those two enantiomers display certain disparities in the pharmacokinetics and tissue distribution, and interact with each other. These findings might be a possible interpretation for the pharmacological and toxic effects of VGB and a potential direction for the development and optimization of the single enantiomer S-VGB.

The role and underlying mechanisms of tumour-derived exosomes in lung cancer metastasis.

PURPOSE OF REVIEW: Lung cancer is one of the most common malignant tumours worldwide. Metastasis is a serious influencing factor for poor treatment effect and shortened survival in lung cancer. But the complicated underlying molecular mechanisms of tumour metastasis remain unclear. In this review, we aim to further summarize and explore the underlying mechanisms of tumour-derived exosomes (TDEs) in lung cancer metastasis. RECENT FINDINGS: TDEs are actively produced and released by tumour cells and carry messages from tumour cells to normal or abnormal cells residing at close or distant sites. Many studies have shown that TDEs promote lung cancer metastasis and development through multiple mechanisms, including epithelial-mesenchymal transition, immunosuppression and the formation of a premetastatic niche. TDEs regulate these mechanisms to promote metastasis by carrying DNA, proteins, miRNA, mRNA, lncRNA and ceRNA. Further exploring TDEs related to metastasis may be a promising treatment strategy and deserve further investigation. SUMMARY: Overall, TDEs play a critical role in metastatic of lung cancer. Further studies are needed to explore the underlying mechanisms of TDEs in lung cancer metastasis.

Strong Ferromagnetic Manipulation of SrTiO3 from CO2 -Straining Effect on Electronic Structure Modulation.

2D magnetic materials are ideal to fabricate magneto-optical, magneto-electric, and data storage devices, which are proposed to be critical to the next generation of information technologies. Benefited from their labile structures, 2D perovskites are amenable for magnetic manipulation through structural optimization. In this work, 2D room-temperature ferromagnetic SrTiO3 is achieved through straining effect induced by supercritical carbon dioxide (SC CO2 ). According to experimental results, the cubic phase of SrTiO3 is converted to tetragonal with exposure of (110), (200), (111), and (211) planes over the SC CO2 treatment, leading to significant ferromagnetic enhancement. Theoretical calculations illustrate that over the conversion from cubic to tetragonal, the electronic structure of SrTiO3 is significantly modulated. Specifically, the spin density of planes of (200), (111), and (211) is enhanced, presumably due to the stabilization of the highest occupied molecular orbital over straining by SC CO2 , leading to magnetic optimizations. This work suggests that magnetic optimization can be achieved from SC CO2 -induced electronic structure modulation.

Lymph Node Metastases in Surgically Resected Solitary Ground-Glass Opacities: A Two-Center Retrospective Cohort Study and Pooled Literature Analysis.

BACKGROUND: An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). PATIENTS AND METHODS: We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter ≤ 3 cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. RESULTS: In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR ≤ 0.5 also had rare LN involvement (0.1%). CONCLUSIONS: From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤ 0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤ 0.5. For the patients with GGO CTR > 0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.

Exposure of ambient PM2.5 during gametogenesis period affects the birth outcome: Results from the project ELEFANT.

Various environmental and behavioural factors influence neonatal health. Gamete formation (gametogenesis) is a crucial period which affects embryo development and neonatal health and ambient air pollution exposure at this stage may lead to an adverse birth outcome. Previous epidemiological and toxicological research demonstrated a strong association between maternal ambient air pollution exposure and adverse birth outcomes. However, the joint exposure-outcome of paternal exposure (76 days before the last menstruation and 14 days after the last menstruation) and maternal exposure (14 days after the last menstruation) when exploring the mechanism of the influence of air pollutants on pregnancy outcome and neonatal health remains unexplored. Here, in the Project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT), we collected the data of 10,960 singleton pregnant women with 24-42 completed gestational weeks and included them in this study. A multinominal logistic regression model was applied to investigate the association between adverse birth outcomes and ambient PM2.5 exposure levels during spermatogenesis and oogenesis. Results from the binary classification of ambient PM2.5 exposure showed that the risk of abnormal birthweight was significantly greater when ambient PM2.5 exposure was both higher during spermatogenesis and oogenesis, with RRs of 1.86 (95% CI: 1.02, 3.39). The risk of macrosomia (RR: 1.88 (95% CI: 1.13, 3.12)) increased significantly when ambient PM2.5 levels were higher during spermatogenesis. Primiparity and primigravity are more likely to be influenced by higher ambient PM2.5 levels during spermatogenesis. In conclusion, more attention should be paid to higher exposure level of ambient PM2.5 during spermatogenesis.

Construct Validity of a Novel Assessment System for Laparoscopic Suture Accuracy Based on Stereoscopy.

BACKGROUND: An accurate and objective measuring tool is lacking for laparoscopic suture accuracy assessment in simulation training. We designed and developed the suture accuracy testing system (SATS) and aimed to determine its construct validity in this study. METHODS: Twenty laparoscopic experts and 20 novices were recruited to perform a suturing task in three sessions using traditional laparoscopic instruments (Tra. session), a handheld multi-degree-of-freedom (MDoF) laparoscopic instrument (MDoF session) and a surgical robot (Rob. session), respectively. The needle entry and exit errors were calculated using the SATS and compared between the two groups. RESULTS: No significant difference of the needle entry error was found in all comparisons. As for the needle exit error, the value of the novice group was significantly higher than that of the expert group in Tra. session (3.48 ± 0.61 mm vs. 0.85 ± 0.14 mm; p = 1.451e-11) and MDoF session (2.65 ± 0.41 mm vs. 1.06 ± 0.17 mm; p = 1.451e-11) but not in Rob. session (0.51 ± 0.12 mm vs. 0.45 ± 0.08 mm; p = 0.091). CONCLUSIONS: The SATS demonstrates construct validity. Surgeons' experience in conventional laparoscopic instruments could be transferred to the MDoF instrument. Surgical robot helps to improve suture accuracy and may bridge the experience gap between laparoscopic experts and novices in basic exercises.

Cornual invasive hydatidiform mole: a rare case report and literature review.

BACKGROUND: The cornual pregnancy is a rare condition of ectopic pregnancies. Invasive hydatidiform mole is a rare form of gestational trophoblastic diseases. Cornual invasive hydatidiform mole is extremely rare. CASE PRESENTATION: A 17-year-old girl presented to the gynecology department with irregular vaginal bleeding. This patient was diagnosed with cornual invasive hydatidiform mole. Mono-chemotherapy was admitted firstly and with poor efficacy. The patient was cured by a combination of chemotherapy and resection of the uterine mass. CONCLUSION: Cases with cornual invasive hydatidiform mole are extremely rare conditions. Unlike common site of invasive hydatidiform mole, mono-chemotherapy may be insufficient for cornual invasive hydatidiform mole. Chemotherapy in combination with other treatments may be needed in this rare condition.

The optimal control chart selection for monitoring COVID-19 phases: a case study of daily deaths in the USA.

Epidemiologists frequently adopt statistical process control tools, like control charts, to detect changes in the incidence or prevalence of a specific disease in real time, thereby protecting against outbreaks and emergent health concerns. Control charts have proven essential in instantly identifying fluctuations in infection rates, spotting emerging patterns, and enabling timely reaction measures in the context of COVID-19 monitoring. This study aims to review and select an optimal control chart in epidemiology to monitor variations in COVID-19 deaths and understand pandemic mortality patterns. An essential aspect of the present study is selecting an appropriate monitoring technique for distinct deaths in the USA in seven phases, including pre-growth, growth, and post-growth phases. Stage-1 evaluated control chart applications in epidemiology departments of 12 countries between 2000 and 2022. The study assessed various control charts and identified the optimal one based on maximum shift detection using sample data. This study considered at Shewhart ($\bar X$, $R$, $C$) control charts and exponentially weighted moving average (EWMA) control chart with smoothing parameters λ = 0.25, 0.5, 0.75, and 1 were all investigated in this study. In Stage-2, we applied the EWMA control chart for monitoring because of its outstanding shift detection capabilities and compatibility with the present data. Daily deaths have been monitored from March 2020 to February 2023. Control charts in epidemiology show growing use, with the USA leading at 42% applications among top countries. During the application on COVID-19 deaths, the EWMA chart accurately depicted mortality dynamics from March 2020 to February 2022, indicating six distinct stages of death. The third and fifth waves were extremely catastrophic, resulting in a considerable loss of life. Significantly, a persistent sixth wave appeared from March 2022 to February 2023. The EWMA map effectively determined the peaks associated with each wave by thoroughly examining the time and amount of deaths, providing vital insights into the pandemic's progression. The severity of each wave was measured by the average number of deaths $W5(1899)\,\gt\,W3(1881)\,\gt\,W4(1393)\,\gt\,W1(1036)\,\gt\,W2(853)\,\gt\,(W6(473)$. The USA entered a seventh phase (6th wave) from March 2022 to February 2023, marked by fewer deaths. While reassuring, it remains crucial to maintain vaccinations and pandemic control measures. Control charts enable early detection of daily COVID-19 deaths, providing a systematic strategy for government and medical staff. Incorporating the EWMA chart for monitoring immunizations, cases, and deaths is recommended.

Transcription Factor E2F8 Promotes Cisplatin Resistance in Hepatocellular Carcinoma by Regulating DNA Damage via NUSAP1.

DNA damage repair has been the key mechanism of cisplatin resistance in hepatocellular carcinoma (HCC). The present study elucidated the molecular mechanism by which nucleolar and spindle-associated protein 1 (NUSAP1) influenced cisplatin tolerance in HCC by regulating DNA damage. First, high mRNA expression of E2F8 and NUSAP1 in HCC was detected by real-time quantitative PCR in cells and tumor tissue. The interaction between E2F8 and NUSAP1 was confirmed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays that E2F8 bound to the promoter region of NUSAP1 and regulated its transcriptional activity. The effects of the E2F8/NUSAP1 axis on cell viability, cell cycle, DNA damage protein γ-H2AX, and cisplatin resistance were investigated by CCK-8, flow cytometry, comet detection, and western blot. The results showed that NUSAP1 knockdown blocked the cell cycle in G0/G1 phase, promoted cisplatin-induced DNA damage, and enhanced cisplatin sensitivity in HCC. Overexpressed E2F8 promoted cell cycle arrest by silencing NUSAP1 in HCC, and promoting DNA damage as well as cisplatin sensitivity. In conclusion, our results suggested that E2F8 enhanced the chemoresistance of HCC cells to cisplatin by activating NUSAP1 to inhibit DNA damage, which provides a basis for describing new therapeutic targets that effectively exacerbate DNA damage and improve the chemical sensitivity of HCC to cisplatin.