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Abstract Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.

Abstract Background Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. Methods We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. Results The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and

Objective Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world. The proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) E670G polymorphism has been reported to be associated with variability in levels of low density lipoprotein cholesterol, a risk factor for CAD. However, the relationship between PCSK9 E670G and CAD is still not fully elucidated. Methods A total of 225 patients and 189 control subjects were recruited in this study. DNA was extracted from peripheral blood samples and was genotyped by mass array method. In addition, we also conducted a meta-analysis of case-control studies to elucidate the relationship of CAD and polymorphism. Results The GG genotype of PCSK9 E670G was associated with a higher risk of CAD [odds ratio (OR) 2.994, 95% confidence interval (CI): 1.174–7.631], even adjusting for risk factors (OR 2.794, 95% CI: 1.215–7.460). Logistic regression analysis showed that the dominant genetic model increased the CAD risk (OR 2.313, 95% CI: 1.070–6.983) after adjusting the confounding factors. Meta-analysis results of 13 studies revealed that PCSK9 E670G polymorphism was correlated with CAD risk under different genetic models. Conclusion Our results demonstrated that PCSK9 E670G genotype was associated with a high risk of CAD.

Background: It is unclear how perioperative hemoglobin decrease (ΔHb) influences the balance between risks and benefits of red blood cell transfusion after cardiac surgery. Methods: We retrospectively analyzed data on 8186 adults who underwent valve surgery and/or coronary artery bypass grafting under cardiopulmonary bypass at two large cardiology centers. We explored the potential association of ΔHb, defined relative to the preoperative level and postoperative nadir, with a composite outcome of in-hospital mortality, myocardial infarction, stroke, and acute kidney injury using multivariable logistic regression, restricted cubic spline, and piecewise-linear models. Results: Among 6316 patients without preoperative anemia, ΔHb ≥ 50 % was associated with an elevated risk of the composite outcome [adjusted odds ratio (aOR) 1.95, 95 % confidence interval (CI) 1.81–2.35]. Among 869 patients without preoperative anemia and with ΔHb ≥ 50 %, postoperative transfusion of no more than four units of red blood cell appeared to decrease the risk of the composite outcome, whereas transfusion of more than six units increased risk. Among 5447 patients without preoperative anemia and with ΔHb < 50 %, postoperative transfusion appeared not to decrease the risk of the composite outcome. Among 1870 patients with preoperative anemia, ΔHb ≥ 30 % significantly increased the risk of the composite outcome (aOR 1.61, 95 % CI 1.23–2.10), and this risk might be moderated by postoperative transfusion of no more than four units of red blood cell, but increased by transfusion of more than six units. Conclusions: ΔHb may influence the balance between risks and benefits of red blood cell transfusion after cardiac surgery.

Abstract Background Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. Methods This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. Results A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p

Abstract Objective Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes. Methods The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated. Results A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h. Conclusion This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications. Trial registration : The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.

Abstract Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.

BackgroundThe efficiency of systemic immune-inflammation index (SII) in predicting prognosis of osteosarcoma (OSA) patients has been extensively analyzed, but no consistent findings are obtained. Therefore, this meta-analysis focused on identifying the precise prognostic value of SII for OSA.MethodsWe comprehensively searched electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 24 February, 2024. Meanwhile, the efficiency of SII in predicting prognosis of OSA was evaluated by calculating pooled hazard ratios (HRs) as well as 95% confidence intervals (CIs). Additionally, the correlation of SII with the OSA clinicopathological characteristics was analyzed based on pooled odds ratios (ORs) and 95%CIs.ResultsSix studies with 1015 cases were enrolled into this work. According to the combined data, the higher SII was markedly related to poor overall survival (OS) (HR=2.01, 95%CI=1.30-3.09, p=0.002) and Enneking stage III (OR=2.21, 95%CI=1.11-4.39, p=0.024) of patients with OSA. Nonetheless, SII was not significantly related to gender, age, pathological fracture, tumor size, tumor location, tumor differentiation, and metastasis in patients with OSA.ConclusionsIn summary, the higher SII is markedly related to poor OS and advanced Enneking stage in OSA patients.Systematic review registrationhttps://inplasy.com/inplasy-2024-7-0107/, identifier INPLASY202470107.

Developmental Endothelial Locus-1 (DEL-1), also known as EGF-like repeat and discoidin I-like domain-3 (EDIL3), is increasingly recognized for its multifaceted roles in immunoregulation and vascular biology. DEL-1 is a protein that is mainly produced by endothelial cells. It interacts with various integrins to regulate the behavior of immune cells, such as preventing unnecessary recruitment and inflammation. DEL-1 also helps in resolving inflammation by promoting efferocytosis, which is the process of clearing apoptotic cells. Its potential as a therapeutic target in immune-mediated blood disorders, cardiovascular diseases, and cancer metastasis has been spotlighted due to its wide-ranging implications in vascular integrity and pathology. However, there are still unanswered questions about DEL-1’s precise functions and mechanisms. This review provides a comprehensive examination of DEL-1’s activity across different vascular contexts and explores its potential clinical applications. It underscores the need for further research to resolve existing controversies and establish the therapeutic viability of DEL-1 modulation.

This paper discusses the reliability deployment of Service Function Chain (SFC) on the hybrid satellite network based on SDN architecture. Firstly, this paper describes the reliability protection problem of SFC, establishes the underlying network and SFC request model, and then establishes the reliability requirement model of network service function and the reliability requirement model of LEO satellite link, and clarifies the optimization goals and constraints. Then, a reliability-based satellite service function chain protection method is proposed, including a reliability protection algorithm based on deep reinforcement learning and a reliability backup algorithm based on LEO satellite node and link. Experiments show that the proposed reliability-based satellite service function chain protection method can improve the SFC request acceptance rate, reduce the average delay, and maintain high request acceptance on hybrid satellite networks based on SDN architecture.

Abstract Background Primary pulmonary artery sarcoma (PAS) is an extremely rare malignant tumor with a poor prognosis. The clinical manifestations of PAS are diverse, including dyspnea, chest pain, cough, and hemoptysis. The poor prognosis is often due to delayed diagnosis caused by similarity in imaging findings with pulmonary thromboembolism (PTE). These cues of diagnosis include the “wall eclipsing sign”, lobulated bulging margins, gadolinium enhancement during MRI imaging, and FDG uptake during PET/CT imaging. However, there are still many misdiagnoses. Case presentation This article reports a woman of reproductive age presenting with a pulmonary artery mass. The computed tomographic pulmonary angiography and positron emission tomography/computed tomography did not show obvious signs of pulmonary artery sarcoma, however, contrast-enhanced echocardiography showed moderate perfusion, which helped differentiate between pulmonary artery sarcoma and pulmonary artery thrombosis, leading to timely surgical treatment. Conclusions PAS is a rare form of cancer that can occasionally be visually similar to PTE on radiographic images. Early diagnosis of PAS is of vital importance to the prognosis of the patients. There are several visual cues that can help differentiate between the two conditions. Additionally, contrast-enhanced echocardiography provides additional information on tumor perfusion, offering another effective approach for a prompt and accurate diagnosis.

Abstract Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy.

Abstract Purpose Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. Methods We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. Results MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). Conclusions Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.

In space-based gravitational wave detection, gravitational wave signals are detected by measuring the Doppler frequency shift of laser exchange between three satellites. Although the laser is pre-stabilized, the laser phase noise is significantly higher than the gravitational wave signal, approximately 7–8 orders of magnitude higher. To reduce the otherwise-overwhelming laser phase noise, the time delay interferometry (TDI) technique is employed by properly time-shifting and linearly combining raw data. Different TDI combinations have various abilities in suppressing laser phase noise, and the response function of gravitational wave signal as well as the power spectral density of noise floor (including test mass acceleration noise and optical path noise) are also different. In this work, we present a unique class of TDI combinations, denoted as [ZX]116,[ZX]216,[ZX]316,[ZX]416, and [ZX]516, which exhibit a distinct geometric space–time diagrams composed of Michelson interferometers as the fundamental constituents. Specifically, when the detector arm lengths are assumed to be equal, these combinations yield response functions and noise power spectral densities of zero. To evaluate the detection performance of these combinations, we investigate their response functions and noise power spectral densities when the detector arm lengths are unequal, and furthermore, derive the analytical expressions for their sensitivity functions. Through our analysis, we have discovered some intriguing results. When the detector arm lengths are unequal, both the response functions and noise spectral densities of these combinations are correlated with the difference in arm lengths L3−L2. However, the sensitivity functions of these TDI combinations remain unaffected by the specific values of the arm length difference, and are consistent with the sensitivity functions of widely-used TDI combinations. For instance, the sensitivity function of [ZX]116 combination is the same as that of the Michelson combination, while the sensitivity functions of [ZX]216 and [ZX]416 combinations match with that of the Sagnac combination. Furthermore, the [ZX]316 and [ZX]516 combinations share the same sensitivity function as the fully symmetric Sagnac combination, enabling the identification of instrument noise and stochastic gravitational wave backgrounds. The discovery of this class of combinations provides support for the diversity of data processing.

Abstract Background To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). Methods Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan–Meier method. Results 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14–103.66), 6.83 (95%CI, 1.08–43.08) and 42.67 (95%CI, 3.66–496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825–0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P

A new species of Anoectochilus (Orchidaceae) from Guangxi, China, A. zhongshanensis, is described here, which was identified based on phylogenetic studies adopting combined plastid markers (rbcL-matK-trnL-F), morphological observation and chemical analysis. Molecular phylogenetic results support the systematic status of A. zhongshanensis as a new species in Anoectochilus genus. Morphologically, this new species is similar to A. zhejiangensis and A. malipoensis, but differs by its characteristic labellum and column, including the hastate or scalpel-shaped lobes of epichile, forward curved and pinnately divided cristate lobes at both sides of the mesochile and inverted triangle column wings. Furthermore, HPLC-ELSD analysis of these three species revealed the interesting chemotaxonomic difference that the principle and characteristic lactone glycoside in this new species was kinsenoside, rather than its diastereoisomer, goodyeroside A, a major glycoside in A. zhejiangensis and A. malipoensis.

Abstract Cost aggregation is crucial to the accuracy of stereo matching. A reasonable cost aggregation algorithm should aggregate costs within homogeneous regions where pixels have the same or similar disparities. Otherwise, the estimated disparity map is prone to the well‐known edge‐fattening issue and the problem of losing fine structures. However, current state‐of‐the‐art convolutional neural networks (CNNs) mainly do cost aggregation with square‐kernel convolutional layers that learn to adjust their kernel elements to make the actual receptive fields of the aggregated costs adapt to homogeneous regions with various shapes. This is a mechanism that easily leads to the above issues due to the translation equivalence and content‐insensitivity properties of CNNs. To tackle these problems, a novel densely connected asymmetric convolution block (Dense‐ACB) based on asymmetric convolutions is proposed to explicitly construct receptive fields with various shapes, which effectively alleviates the issues caused by mismatching shapes of receptive fields and homogeneous regions. The proposed Dense‐ACB brings new insight to CNN‐based stereo matching networks. Based on the proposed cost aggregation method, an efficient and effective stereo matching network is built, which not only achieves competitive overall accuracy compared with state‐of‐the‐art models but also effectively alleviates the edge‐fattening problem and preserves fine structures.

The long-distance migration of Oncomelania snails mainly occurs by attaching to floating objects during floods. However, the processes, characteristics and effects of migration are not fully understood. Here, a motion equation for floating objects with attached Oncomelania snails was constructed using the Lagrangian method. The equation can be numerically solved to simulate the movement of floating objects after parameter calibration. Then, the calibrated parameters were used to simulate the migration of Oncomelania snails in the lower Jingjiang River, where they had spread over a large area. The effects of flood conditions on the migration and spread of Oncomelania snails have been studied to a certain extent, but the impact of wind conditions on snail migration has rarely been reported. Therefore, based on the distribution of Oncomelania snails in China, the difficulties and key areas for the control of schistosomiasis and Oncomelania snails, and the morphological characteristics of the river reach, the Lower Jingjiang River section was selected as a practical application case. A theoretical model of the migration and spread of Oncomelania snails was established, and the characteristics of the Oncomelania snail migration were simulated and analyzed based on flood and distribution patterns under different wind conditions. The results indicate that wind conditions have little influence on the longitudinal spreading of Oncomelania snails but have a relatively large influence on the lateral spreading of snails. Compared with calm wind conditions, both northeasterly and southerly wind conditions can lead to longer longitudinal migration distances of snails, thereby increasing the risk of snail spreading and schistosomiasis transmission.

Heavy metal dynamics at the sediment-water interface (SWI) has attracted plenty of attention due to their meticulous depiction for metal sorption-release processes. However, little is known about their concentration, migration and release characteristics underneath the ice, especially at the millimeter scale. Here we investigated dynamics of labile As, Cd, Cu, Mn, Pb and Zn by the diffusive gradients in thin-films (DGT) technique during ice-covered and ice-free periods in the Lake Xingkai basin. The concentrations of metals were relatively high at the SWI and ranged for As: 0.001~13.42 μg L−1, Cd: 0.01~0.45 μg L−1, Cu: 0.001~2.75 μg L−1, Mn: 5.31~2958.29 μg L−1, Pb: 0.06~1.43 μg L−1, and Zn: 2.92~112.96 μg L−1. Particularly, concentration of Mn was extremely higher than other studies, possibly due to diagenetic process. Labile concentrations of heavy metals in January were significantly lower than those in May, suggesting that elevated temperatures lead to the release of heavy metals from the sediment to the overlying water. Based on the Fick’s first law, the diffusive fluxes as a source of Mn (413.82-1163.25 mg·m-2·d-1) and As (3.53 -8.12 mg·m-2·d-1) indicated that heavy metals were released from sediments to the overlying water. While the diffusive fluxes as a sink of Zn (-1.80-(-2.36) mg·m-2·d-1) and Pb (-0.02-(-0.46) mg·m-2·d-1) to sediments. Redundancy Analysis (RDA) revealed that the main factors influencing the heavy metal migration were dissolved oxygen (45.6% of total explanation, P=0.01) in January, and water temperature (52.9%, P=0.006) in May. This study extends theoretical scope for understanding metal migration and release process, and provides valuable suggestions for lake management during the freezing period.