[MiRNA-103-3p promotes neural cell autophagy by activating Wnt/ß-catenin signaling via targeting rab10 in a rat model of depression].

OBJECTIVE: To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect. METHODS: Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress (CUMS) groups (n=12). The rats in the latter 3 groups were subjected to injections of normal saline, an adeno-associated viral (AAV) vector, or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling. The depressive behavioral changes of the rats were assessed using behavioral tests. The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites. The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation (RIP) assay. The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay. In corticosterone-stimulated PC12 cells, the changes in BDNF, CREB, p62, Beclin-1, Wnt3a, Gsk3ß, phosphorylated (p)-Gsk3ß, and ß-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor, alone or in combination, were analyzed using qRT-PCR and Western blotting. RESULTS: Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats. The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosteronestimulated PC12 cells. Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10. In PC12 cells, overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/ß-catenin signaling pathway, up-regulated the expressions of BDNF, CREB and Beclin-1, and down-regulated the expression of p62 protein; silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor. CONCLUSION: In mouse models of depression, miRNA-103-3p activates Wnt/ß-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

[Rethinking the scope of lymphadenectomy after neoadjuvant immunotherapy for locally advanced gastric cancer].

Radical gastrectomy is the core of comprehensive treatment for patients with locally advanced gastric cancer,while reasonable and standardized lymphadenectomy is the key to radical gastrectomy.With the continuous development of treatment methods and therapeutic drugs for advanced gastric cancer, it is worth exploring whether the scope of lymphadenectomy needs to be changed. Neoadjuvant immunotherapy has brought a new breakthrough for locally advanced gastric cancer, increased pathological complete response rate, reduced clinical stage of tumors, and increased radical surgical resection rate, but it has not brought long-term benefits to patients. Lymph nodes play an important role in human anti-tumor immune response, and some basic studies suggest that preserving some normal lymph nodes may be more helpful to enhance the efficacy of immunotherapy. Thus, in the era of immunotherapy, the extent of lymph node dissection for locally advanced gastric cancer needs to balance continuous drug benefits, patient quality of life, and survival benefits, awaiting further high-quality clinical research for determination. Questions such as how to differentiate between normal and metastatic lymph nodes, how to rationally preserve normal lymph nodes, and whether preserving partial lymph node function can lead to greater benefits for patients from immunotherapy warrant further exploration.

Physics-Informed Online Learning for Temperature Prediction in Metal AM.

In metal additive manufacturing (AM), precise temperature field prediction is crucial for process monitoring, automation, control, and optimization. Traditional methods, primarily offline and data-driven, struggle with adapting to real-time changes and new process scenarios, which limits their applicability for effective AM process control. To address these challenges, this paper introduces the first physics-informed (PI) online learning framework specifically designed for temperature prediction in metal AM. Utilizing a physics-informed neural network (PINN), this framework integrates a neural network architecture with physics-informed inputs and loss functions. Pretrained on a known process to establish a baseline, the PINN transitions to an online learning phase, dynamically updating its weights in response to new, unseen data. This adaptation allows the model to continuously refine its predictions in real-time. By integrating physics-informed components, the PINN leverages prior knowledge about the manufacturing processes, enabling rapid adjustments to process parameters, geometries, deposition patterns, and materials. Empirical results confirm the robust performance of this PI online learning framework in accurately predicting temperature fields for unseen processes across various conditions. It notably surpasses traditional data-driven models, especially in critical areas like the Heat Affected Zone (HAZ) and melt pool. The PINN's use of physical laws and prior knowledge not only provides a significant advantage over conventional models but also ensures more accurate predictions under diverse conditions. Furthermore, our analysis of key hyperparameters-the learning rate and batch size of the online learning phase-highlights their roles in optimizing the learning process and enhancing the framework's overall effectiveness. This approach demonstrates significant potential to improve the online control and optimization of metal AM processes.

[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].

Objective: The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. Methods: The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (ß3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and ß3 in platelets were analyzed by Western blot. Results: Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and ß3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the ß-propeller domain of the p.S160-S192 deletion lost two ß-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a ß chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of ß3 was 11.36% of the normal level. Conclusion: The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

[Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in the mobilization of autologous peripheral blood stem cells in patients with multiple myeloma].

Objective: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

[Effectiveness and safety of multimodal analgesia in open gastrostomy in patients with end-stage head and neck cancer].

Objective: To investigate the effectiveness and safety of multimodal analgesia in patients with end-stage head and neck cancer in open gastrostomy surgery. Methods: This was a randomized controlled trial. From June to December 2023, 50 patients with end-stage head and neck cancer who underwent elective open gastrostomy surgery in Beijing Tongren Hospital Affiliated to Capital Medical University were prospectively selected. The patients were divided into multimodal analgesia group and local anesthesia group using the random number table method according to different anesthesia methods, with 25 cases in each group. In multimodal analgesia group, a multimodal analgesia regimen was adopted: ultrasound-guided abdominal wall nerve block (rectus sheath block and transverse abdominis plane block)+intravenous injection of oxycodone+intravenous injection of flurbiprofen axetil and dexamethasone. In local anesthesia group, local infiltration anesthesia with ropivacaine was adopted. The main outcome measure was the incidence of intraoperative pain numeric rating scale (NRS) score>3 points in the two groups. The secondary observation indicators included NRS score and hemodynamic indexes [mean arterial pressure (MAP) and heart rate (HR)] at various time points during surgery [before anesthesia (T0), at the time of incision (T1), 10 minutes after surgery (T2), during gastric body traction (T3), and at the end of surgery (T4)], incidence of adverse reactions, postoperative patient satisfaction score, as well as the NRS scores at rest and activity (coughing) within 24 hours after surgery. Results: The multimodal analgesia group included 21 males and 4 females, aged (61.4±9.9) years. There were 19 males and 6 females in the local anesthesia group, aged (58.6±10.8) years. The incidence of intraoperative NRS score>3 points and the incidence of salvage analgesia in the multimodal analgesia group were both 12.0% (3/25), which were lower than 60.0% (15/25) in the local anesthesia group, and the differences were statistically significant (all P<0.001); The NRS score [M (Q1, Q3)] at T3 in the multimodal analgesia group was 2 (2, 3) points, which were lower than 5 (3, 6) points in the local anesthesia group (P<0.05). There were smaller variabilities in MAP and HR in the multimodal analgesia group than those in the local anesthesia group (all P<0.05). The incidence of intraoperative tachycardia, surgical traction reaction, and nausea in the multimodal analgesia group was lower than that in the local anesthesia group (all P<0.05). The postoperative satisfaction score of patients in the multimodal analgesia group was (9.25±0.71) points, which were higher than (7.33±0.87) points in the local anesthesia group (P<0.001). NRS score during postoperative activity within 24 hours in the multimodal analgesia group were (2.36±0.75) points, which were lower than (3.03±0.81) points of the local anesthesia group (P=0.005). No adverse reactions such as urinary retention, nausea, vomiting and dizziness occurred in both groups. Conclusion: Compared with local anesthesia, the multimodal analgesic strategy could provide better analgesic effect and longer duration, better hemodynamic stability, and fewer intraoperative adverse reactions in patients with end-stage head and neck cancer undergoing open gastrostomy.

Clinical application of endoscopic submucosal dissection for superficially invasive squamous cell carcinoma/high-grade squamous intraepithelial lesion involving the canal anal.

BACKGROUND: Superficially invasive squamous cell carcinoma (SISCC) and high-grade squamous intraepithelial lesions (HSIL) involving the anal canal are rare, and their surgical management involves local excision. Endoscopic submucosal dissection (ESD) has recently emerged as a promising treatment. This study aimed to evaluate the feasibility and safety of ESD for SISCC and HSIL in the anal canal. METHODS: All patients diagnosed with SISCC or HSIL in the anal canal who underwent ESD between November 2018 and May 2023 were included. Patient age, sex, pathology, human immunodeficiency virus (HIV) status, human papillomavirus (HPV) status, T stage, en bloc rate, and R0 resection rate were analyzed. RESULTS: Ten patients, including two men and eight women, with a median age of 61 (51-68) years were enrolled. All patients were HIV-negative, but five (50%) were HPV-positive. Pathological examination showed tumor stage of two patients as T2, one as T0 of SISCC, and seven as Tis of HSIL. The median specimen and tumor sizes were 24 (6-65) mm and 18 (6-55) mm, respectively. The en bloc and R0 resection rates were 100% and 80%, respectively. No severe complications occurred and no recurrence was observed at the follow-up (median follow-up period, 9 (1-35) months). CONCLUSIONS: ESD is a reliable and minimally invasive procedure that enables more individualized treatment options for specific groups. As we were limited by the length of the observation period, the long-term performance of ESD for SISCC and HSIL involving the anal canal requires further investigation.

Retraction Note: Study on the expression and mechanism of inflammatory factors in the brain of rats with cerebral vasospasm.

The article "Study on the expression and mechanism of inflammatory factors in the brain of rats with cerebral vasospasm" by Q. Huang, G. Wang, Y.-L. Hu, J.-X. Liu, J. Yang, S. Wang, H.-B. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (12): 2887-2894 - PMID: 28682429 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/48E37B385D83F1B09741B2B06B39C3), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive and have not provided the study's raw data. The journal's investigation uncovered a duplication between Figure 2A and Figure 1D with a previously published article (https://doi.org/10.1371/journal.pone.0096212). Additionally, duplications were identified between panels b, c, d, f, g, and h of Figure 3A and Figure 6B, C, D, F, G, and H, respectively, of the same previously published article (https://doi.org/10.1371/journal.pone.0096212). Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12948.

How lignin biosynthesis responds to nitrogen in plants: a scoping review.

Nitrogen (N) plays a critical role in the functioning of key amino acids and synthetic enzymes responsible for the various stages of lignin biosynthesis. However, the precise mechanisms through which N influences lignin biosynthesis have not been fully elucidated. This scoping review explores how lignin biosynthesis responds to N in plants. A systematic search of the literature in several databases was conducted using relevant keywords. Only 44 of the 1842 selected studies contained a range of plant species, experimental conditions, and research approaches. Lignin content, structure, and biosynthetic pathways in response to N are discussed, and possible response mechanisms of lignin under low N are proposed. Among the selected studies, 64.52% of the studies reter to lignin content found a negative correlation between N availability and lignin content. Usually, high N decreases the lignin content, delays cell lignification, increases p-hydroxyphenyl propane (H) monomer content, and regulates lignin synthesis through the expression of key genes (PAL, 4CL, CCR, CAD, COMT, LAC, and POD) encoding miRNAs and transcription factors (e.g., MYB, bHLH). N deficiency enhances lignin synthesis through the accumulation of phenylpropanoids, phenolics, and soluble carbohydrates, and indirect changes in phytohormones, secondary metabolites, etc. This review provides new insights and important references for future studies on the regulation of lignin biosynthesis.

[Comparison of the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery].

Objective: To compare the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery. Methods: Prospectively, 60 pediatric patients, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, scheduled to undergo binocular strabismus daytime surgery in Beijing Tongren Hospital under general anesthesia with laryngeal mask airway from December 2021 to May 2022 were selected. They were randomly divided into Remimazolam group and Propofol group with 30 cases in each group, according to the ratio of 1∶1 by SPSS program. Patients in Remimazolam group were induced by remimazolam, remifentanil and micuronium chloride, and maintained by remimazolam and remifentanil. Patients in Propofol group were induced by propofol, remifentanil and micuronium chloride, and maintained by propofol and remifentanil. Patients in Remimazolam group were given 0.1 mg of flumazenil for antagonism 3 minutes after operation, while children in Propofol group waited for natural awakening. The primary outcome was the time from drug withdrawal to laryngeal mask removal after operation. The secondary outcomes included the time for consciousness loss during induction, intraoperative hemodynamic data [mean arterial pressure (MAP) and heart rate], the success rate of sedation, the awareness rate during operation, and the incidence of adverse events after admission to postanesthesia care unit(PACU). Results: The Remimazolam group included 12 males and 18 females, aged (5.0±1.4) years. There were 14 males and 16 females in the Propofol group, aged (5.3±1.3) years. The time from drug withdrawal to laryngeal mask removal in Remimazolam group was (6.5±1.2) min, which was shorter than that in Propofol group of (10.7±1.9) min (P<0.001). The time for consciousness loss during induction was (38.1±4.8) s in Remimazolam group, which was longer than that in Propofol group of (31.6±4.9) s (P<0.001). The variability of MAP and heart rate of patients during operation in Remimazolam group was lower than that in Propofol group (all P<0.05). There was no significant difference in sedation success rate, intraoperative awareness and adverse reactions in PACU between the two groups (all P>0.05). Conclusion: In pediatric patients with binocular strabismus during daytime surgery, general anesthesia with remimazolam can shorten the time from drug withdrawal to laryngeal mask removal after operation without increasing the incidence of postoperative adverse reactions and can provide more stable hemodynamics.

[Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection].

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (ß [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Novel circular RNA Sestrin1 promotes chicken myoblast proliferation and differentiation via circSesn1/miR-16-5p/SESN1 pathway.

1. The development of chicken skeletal muscle is directly relevant to poultry husbandry production. Numerous studies have suggested that circular RNA play pivotal roles in muscle development. However, the functions and mechanisms of most circRNA in chicken myogenesis remain largely unknown.2. This study identified a novel circSESN1 based on existing sequencing data and examined its authenticity and subcellular localisation by enzyme digestion and RNA fluorescence in situ hybridisation. Additionally, there was a positive correlation between the expression levels of circSESN1 and the developmental stage of chicken muscle.3. Mechanistically, knockdown or overexpression of circSESN1 was performed in primary myoblasts to validate its function. The interactions between circSESN1, miR-16-5p, and the target gene sestrin 1 (SESN1) were investigated using bioinformatics analysis and a dual fluorescein reporter system. Real-time qPCR, a cell proliferation assay, and immunofluorescence staining techniques were used to investigate the promotion effect of circSESN1 on myoblast proliferation and differentiation by miR-16-5p/SESN1 pathway.4. The results demonstrated that the newly identified chicken circSESN1 directly sponges gga-miR-16-5p to regulate SESN1 gene expression, promoting myoblast proliferation and differentiation.

[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[The Development of SpCas9 Variants with High Specificity and Efficiency Based on the HH Theory].

Streptococcus pyogenes Cas9 (SpCas9) is the most popular tool in gene editing; however, off-target mutagenesis is one of the biggest impediments in its application. In our previous study, we proposed the HH theory, which states that sgRNA/DNA hybrid (hybrid) extrusion-induced enhancement of hydrophobic interactions between the hybrid and REC3/HNH is a key factor in cleavage initiation. Based on the HH theory, we analyzed the interactions between the REC3 domain and hybrid and obtained 8 mutant sites. We designed 8 SpCas9 variants (V1-V8), used digital droplet PCR to assess SpCas9-induced DNA indels in human cells, and developed high-fidelity variants. Thus, the HH theory may be employed to further optimize SpCas9-mediated genome editing systems, and the resultant V3, V6, V7, and V8 SpCas9 variants may be valuable for applications requiring high-precision genome editing.

Improved cut weight predictions from DEXA scans of lamb carcasses enables more accurate allocation of cuts to processing plans.

The value of precise dual energy X-ray absorptiometry (DEXA) cut weight predictions to lamb allocation to cut plans is unknown. Lambs (n = 191) varying in carcase weight (HSCW) and GR (tissue depth over the 12th rib) were DEXA scanned and boned out to weigh retail cuts. Cut weights were predicted using HSCW; HSCW + GR; HSCW + DEXA and HSCW + DEXA image components in GLM models. DEXA improved cut weight predictions in most cuts (P < 0.05). A dataset of 10,000 carcases was then simulated using the associations between HSCW, GR and cut weights, before being truncated to 4500 lambs representing onel day's HSCW distribution. A lamb Carcase Optimisation Tool scenario was developed with 2-3 cut options per carcase section and cut weight thresholds applied to several cuts. Processing costs, market values and actual cut weights were input into the Optimiser to determine carcase allocation to cut options for optimised profits. This scenario was repeated using the predicted cut weights to determine the cut misallocations caused. DEXA-predicted cut weights produced 16.7% and 8.0% less misallocations than HSCW and GR. DEXA produced 20.8% and 14.3% less misallocations than HSCW and GR in shortloins, and 25.5% and 12.9% less in hindquarters. While cut misallocations have little direct impact on total profits, as product is over and under-valued when misallocated, reducing cut misallocations will improve processor compliance when sorting carcases into cut plans- reducing their need to retrim, downgrade and repackage product or the erosion of customer confidence caused by supplying product not meeting market specifications.

Climate warming accelerates carbon release from foliar litter-A global synthesis.

With over one-third of terrestrial net primary productivity transferring to the litter layer annually, the carbon release from litter serves as a crucial valve in atmospheric carbon dioxide concentrations. However, few quantitative global projections of litter carbon release rate in response to climate change exist. Here, we combined a global foliar litter carbon release dataset (8973 samples) to generate spatially explicitly estimates of the response of their residence time (τ) to climate change. Results show a global mean litter carbon release rate ( k $$ k $$ ) of 0.69 year-1 (ranging from 0.09-5.6 year-1). Under future climate scenarios, global mean τ is projected to decrease by a mean of 2.7% (SSP 1-2.6) and 5.9% (SSP 5-8.5) during 2071-2100 period. Locally, the alleviation of temperature and moisture restrictions corresponded to obvious decreases in τ in cold and arid regions, respectively. In contract, τ in tropical humid broadleaf forests increased by 4.6% under SSP 5-8.5. Our findings highlight the vegetation type as a powerful proxy for explaining global patterns in foliar litter carbon release rates and the role of climate conditions in predicting responses of carbon release to climate change. Our observation-based estimates could refine carbon cycle parameterization, improving projections of carbon cycle-climate feedbacks.

Comprehensive analysis of changes in expression of lncRNA, microRNA and mRNA in liver tissues of chickens with high or low abdominal fat deposition.

1. The liver of chickens is a dominant lipid biosynthetic tissue and plays a vital role in fat deposition, particularly in the abdomen. To determine the molecular mechanisms involved in its lipid metabolism, the livers of chickens with high (H) or low (L) abdominal fat content were sampled and sequencing on long non-coding RNA (lncRNA), messenger RNA (mRNA) and small RNA (microRNA) was performed.2. In total, 351 expressed protein-coding genes for long non-coding RNA (DEL; 201 upregulated and 150 downregulated), 400 differentially expressed genes (DEG; 223 upregulated and 177 downregulated) and 10 differentially expressed miRNA (DEM; four upregulated and six downregulated) were identified between the two groups. Multiple potential signalling pathways related to lipogenesis and lipid metabolism were identified via pathway enrichment analysis. In addition, 173 lncRNA - miRNA - mRNA interaction regulatory networks were identified, including 30 lncRNA, 27 mRNA and seven miRNA.3. These networks may help regulate lipid metabolism and fat deposition. Five promising candidate genes and two lncRNA may play important roles in the regulation of adipogenesis and lipid metabolism in chickens.

Critical Values of Daily Sedentary Time and Its Longitudinal Association with Mild Cognitive Impairment Considering APOE ε4: A Prospective Cohort Study.

BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.

Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

[Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery].

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.