Integrating hydrogels manipulate ECM deposition after spinal cord injury for specific neural reconnections via neuronal relays.

A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRß+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Perphenazine modified pillar[5]arene based nano-assemblies for synergistic photothermal and photodynamic cancer therapy.

Nano-assemblies based on perphenazine modified pillar[5]arene were constructed successfully for synergistic photothermal and photodynamic (I&II) cancer therapy.

In-situ revealed inhibition of W2C to excessive oxidation of CoOOH for high-efficiency alkaline overall water splitting.

The design of low-cost, efficient, and stable multifunctional basic catalysts to replace the high-cost noble metal catalysts remains a challenge. In this work, we report a dual-component Co-W2C catalytic system which achieves excellent properties of hydrogen evolution reaction (HER, η10 = 63 mV), oxygen evolution reaction (OER, η10 = 259 mV) and overall water splitting (η10 = 1.53 V) by adjusting the interfacial electronic structure of the material. Further density functional theory (DFT) calculations indicate that the efficient electronic modulation at the W2C/Co interface leads to the generation of favorable hydroxyl and hydrogen species energetics on the hybrid surface. The results of the in-situ Raman spectra show that W2C can suppress the excessive oxidation of the active site during the OER process, and the existence of core-shell structure also protects the W2C substrate. The stable and efficient catalytic performance of Co-W2C is attributed to the common advantages of structural and interface manipulation.

Predictors of post-healing recurrence in patients with diabetic foot ulcers: A systematic review and meta-analysis.

BACKGROUND: Diabetic foot ulcer is one of the most prevalent, serious, and costly consequences of diabetes, often associated with peripheral neuropathy and peripheral arterial disease. These ulcers contribute to high disability and mortality rates in patients and pose a major challenge to clinical management. OBJECTIVE: To systematically review the risk prediction models for post-healing recurrence in diabetic foot ulcer (DFU) patients, so as to provide a reference for clinical staff to choose appropriate prediction models. METHODS: The authors searched five databases (Cochrane Library, PubMed, Web of Science, EMBASE, and Chinese Biomedical Database) from their inception to September 23, 2023, for relevant literature. After data extraction, the quality of the literature was evaluated using the Predictive Model Research Bias Risk and Suitability Assessment tool (PROBAST). Meta-analysis was performed using STATA 17.0 software. RESULTS: A total of 9 studies involving 5956 patients were included. The recurrence rate after DFU healing ranged from 6.2 % to 41.4 %. Nine studies established 15 risk prediction models, and the area under the curve (AUC) ranged from 0.660 to 0.940, of which 12 models had an AUC≥0.7, indicating good prediction performance. The combined AUC value of the 9 validation models was 0.83 (95 % confidence interval: 0.79-0.88). Hosmer-Lemeshow test was performed for 10 models, external validation for 5 models, and internal validation for 6 models. Meta-analysis showed that 14 predictors, such as age and living alone, could predict post-healing recurrence in DFU patients (p < 0.05). CONCLUSION: To enhance the quality of these risk prediction models, there is potential for future improvements in terms of follow-up duration, model calibration, and validation processes.

Effectiveness of mHealth intervention for trismus exercise in patients with head and neck cancer undergoing proton and heavy ion therapy: a randomized control trial.

PURPOSE: This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise compliance, and self-efficacy in patients receiving proton and heavy ion therapy for head and neck cancer. METHODS: This open-label, parallel-group, randomized, superiority trial involved a self-developed "Health Enjoy System" intervention. We assessed maximal mouth opening, exercise compliance, and self-efficacy at baseline (T0), post-treatment (T1), and at 1 month (T2) and 3 months (T3) after radiotherapy. Generalized estimating equations were used to analyze differences between the groups over time, with results reported as P values and 95% confidence intervals (CIs). RESULTS: The study included 44 participants. At T3, the intervention group showed a 6 mm greater increase in maximal interincisal opening than the control group (mean difference = 6.0, 95% CI = 2.4 to 9.5, P = 0.001). There was also a significant difference in exercise compliance between the groups (mean difference = 31.7, 95% CI = 4.6 to 58.8, P = 0.022). However, no significant difference in self-efficacy was found between the groups. CONCLUSION: This study demonstrated that an mHealth intervention incorporating behavior change theory could effectively enhance or maintain maximal mouth opening in patients undergoing proton and heavy ion therapy for head and neck cancer in China. This approach provides valuable support during and after treatment. TRIAL REGISTRATION: ChiCTR: ChiCTR2300067550. Registered 11 Jan 2023.

Fluorescence-enhanced supra-amphiphiles based on pillar[5]arene: construction, controllable self-assembly and application in cell imaging.

Fluorescence-enhanced supra-amphiphiles based on (WP5)2⊃ENDTn were constructed successfully. When n = 9, they can self-assemble into uniform micelles with an average diameter of about 90 nm and be further applied in cell imaging.

Global incidence and characteristics of spinal cord injury since 2000-2021: a systematic review and meta-analysis.

BACKGROUND: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. METHODS: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. RESULTS: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50-26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15-28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25-35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. CONCLUSIONS: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.

Risk prediction models for intensive care unit-acquired weakness in critically ill patients: A systematic review.

BACKGROUND: Intensive care unit (ICU)-acquired weakness (ICU-AW) is a critical complication that significantly worsens patient prognosis. It is widely thought that risk prediction models can be harnessed to guide preventive interventions. While the number of ICU-AW risk prediction models is increasing, the quality and applicability of these models in clinical practice remain unclear. OBJECTIVE: The objective of this study was to systematically review published studies on risk prediction models for ICU-AW. METHODS: We searched electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database) from inception to October 2023 for studies on ICU-AW risk prediction models. Two independent researchers screened the literature, extracted data, and assessed the risk of bias and applicability of the included studies. RESULTS: A total of 2709 articles were identified. After screening, 25 articles were selected, encompassing 25 risk prediction models. The area under the curve for these models ranged from 0.681 to 0.926. Evaluation of bias risk indicated that all included models exhibited a high risk of bias, with three models demonstrating poor applicability. The top five predictors among these models were mechanical ventilation duration, age, Acute Physiology and Chronic Health Evaluation II score, blood lactate levels, and the length of ICU stay. The combined area under the curve of the ten validation models was 0.83 (95% confidence interval: 0.77-0.88), indicating a strong discriminative ability. CONCLUSIONS: Overall, ICU-AW risk prediction models demonstrate promising discriminative ability. However, further optimisation is needed to address limitations, including data source heterogeneity, potential biases in study design, and the need for robust statistical validation. Future efforts should prioritise external validation of existing models or the development of high-quality predictive models with superior performance. REGISTRATION: The protocol for this study is registered with the International Prospective Register of Systematic Reviews (registration number: CRD42023453187).

Effects of intravenous lidocaine on postoperative pain and gastrointestinal function recovery following gastrointestinal surgery: a meta-analysis.

INTRODUCTION: The full extent of intravenous lidocaine's effectiveness in alleviating postoperative pain and enhancing gastrointestinal function recovery remains uncertain. EVIDENCE ACQUISITION: We conducted an exhaustive search of databases to identify randomized controlled trials that compared intravenous lidocaine infusion's efficacy to that of a placebo or routine care in patients undergoing gastrointestinal surgery. The primary outcome measure was resting pain scores 24 h postoperatively. We utilized a random-effects model based on the intention-to-treat principle for the overall results. EVIDENCE SYNTHESIS: This study included twenty-four trials with 1533 patients. Intravenous lidocaine significantly reduced resting pain scores 24 h after gastrointestinal surgery (twenty trials, SMD -0.67, 95% CI -1.09 to -0.24, P=0.002, I2 = 90%). This finding was consistent in subgroup analyses and sensitivity analyses. The benefit was also observed at other resting and moving time points (1, 2, 4, and 12 h) postoperatively. Intravenous lidocaine significantly decreased opioid consumption within 24 h after surgery (eleven trials, SMD: -1.19; 95% CI: -1.99 to -0.39; P=0.003). Intravenous lidocaine also shortened the time to bowel sound (MD: -8.51; 95% CI: -14.59 to -2.44; P=0.006), time to first flatus (MD: -6.00; 95% CI: -9.87 to -2.13; P=0.002), and time to first defecation (MD: -9.77; 95% CI: -17.19 to -2.36; P=0.01). CONCLUSIONS: Perioperative intravenous lidocaine can alleviate acute pain and expedite gastrointestinal function recovery in patients undergoing gastrointestinal surgery. However, the results should be interpreted with caution due to substantial heterogeneity. Further large-scale studies are necessary to validate these findings.

MRI-Based Prediction of Clinical Improvement Following Ventricular Shunt Placement for Normal Pressure Hydrocephalus (NPH): Development and Evaluation of an Integrated Multi-Sequence Machine Learning Algorithm.

BACKGROUND AND PURPOSE: Symptoms of normal pressure hydrocephalus (NPH) are sometimes refractory to shunt placement, with limited ability to predict improvement for individual patients. We evaluated an MRI-based artificial intelligence method to predict post-shunt NPH symptom improvement. MATERIALS AND METHODS: NPH patients who underwent magnetic resonance imaging (MRI) prior to shunt placement at a single center (2014-2021) were identified. Twelve-month post-shunt improvement in modified Rankin Scale (mRS), incontinence, gait, and cognition were retrospectively abstracted from clinical documentation. 3D deep residual neural networks were built on skull stripped T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Predictions based on both sequences were fused by additional network layers. Patients from 2014-2019 were used for parameter optimization, while those from 2020-2021 were used for testing. Models were validated on an external validation dataset from a second institution (n=33). RESULTS: Of 249 patients, n=201 and n=185 were included in the T2-based and FLAIR-based models according to imaging availability. The combination of T2-weighted and FLAIR sequences offered the best performance in mRS and gait improvement predictions relative to models trained on imaging acquired using only one sequence, with AUROC values of 0.7395 [0.5765-0.9024] for mRS and 0.8816 [0.8030-0.9602] for gait. For urinary incontinence and cognition, combined model performances on predicting outcomes were similar to FLAIR-only performance, with AUROC values of 0.7874 [0.6845-0.8903] and 0.7230 [0.5600-0.8859]. CONCLUSIONS: Application of a combined algorithm using both T2-weighted and FLAIR sequences offered the best image-based prediction of post-shunt symptom improvement, particularly for gait and overall function in terms of mRS. ABBREVIATIONS: NPH = normal pressure hydrocephalus; iNPH = idiopathic NPH; sNPH = secondary NPH; AI = artificial intelligence; ML = machine learning; CSF = cerebrospinal fluid; AUROC = area under the receiver operating characteristic; FLAIR = fluid attenuated inversion recovery; BMI = body mass index; CCI = Charlson Comorbidity Index; SD = standard deviation; IQR = interquartile range.

CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.

Genomic Sequencing and Analysis of Enzootic Nasal Tumor Virus Type 2 Provides Evidence for Recombination within the Prevalent Chinese Strains.

In recent years, the clinical cases of ENTV-2 infection have increased and become prevalent in several provinces of China. In this study, we reported the occurrence of ENTV-2 in one goat farm in Chongqing, southwest China. The complete genome of an emerged ENTV-2 isolate (designated as CQ2) was sequenced with 7468 bp in length. Phylogenetic analysis revealed that ENTV-2 consisted of two main lineages. Lineage 1 was composed of Chinese strains and could be subdivided into five sublineages. CQ2 and the other six recent isolates from China were clustered in sublineage 1.5; however, CQ2 was significantly different from the other six isolates. Furthermore, recombination analysis suggested that CQ2 might be a recombinant variant derived from sublineage 1.5 and sublineage 1.2 strains, with the recombination region in areas of pro and pol genes. In conclusion, we sequenced and analyzed the complete genome of a potential ENTV-2 recombinant, which may contribute to our understanding of the genetic variation and evolution of ENTV-2 in China.

Comparison of multiple preservation and digestion methods for determination of tungsten concentrations in environmental media using ICP-MS.

Tungsten is an emerging environmental pollutant. However, a proved robust method for preserving and determining the concentrations of tungsten in environmental media is still lacking. This study examined and compared the suitability of classic methods and previously reported tungsten-oriented methods on preserving dissolved tungsten and recovering tungsten from soil/sediment matrix. Tungsten concentrations in the water samples and digestates were then determined by inductively coupled plasma mass spectrometry. Our data showed that the tungsten-oriented HF and alkaline preservatives indeed successfully maintained the stability of dissolved tungsten. Even when preserved using HNO3 or HCl, dissolved tungsten concentrations did not notably change in most of our water samples over the course of ∼4 months. Using glass containers for storing water samples also did not produce much difference from using high-density polyethylene containers. Our data further suggested that the addition of HF in digestion was important for tungsten solubilization from soil/sediment matrix. The digestion methods with HNO3/HCl/HF and HNO3/HF/NH4OH/EDTA both yielded quantitative recoveries of tungsten from certified reference materials and known synthetic samples, while the other tested methods had limited recoveries. The methods validated by this study could be used to accurately determine tungsten concentrations in environmental media and thereby to assess the fate and potential risks of tungsten.

Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

Altered regional brain activity and functional connectivity in primary intravaginal anejaculation patients revealed by resting-state fMRI.

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

Two new species of Perenniporia sensu lato (Polyporales, Basidiomycota) from China and two new combinations in Crassisporus.

Phylogenetic and morphological analyses on Perenniporia s.l. were carried out. Phylogenies on Perenniporia s.l. are reconstructed with two loci DNA sequences including the internal transcribed spacer (ITS) regions and the large subunit (nLSU). Two new species from Yunnan Province, southwest China, Perenniporiaprunicola and P.rosicola in Perenniporia s.l., are illustrated and described. Perenniporiaprunicola is characterised by the perennial and resupinate basidiomata with a clay pink pore surface when fresh, a trimitic hyphal system, the presence of clavate to fusiform hymenial cystidia, ellipsoid to broadly ellipsoid basidiospores measuring 4.8-6.2 × 3.6-4.5 µm. Perenniporiarosicola is characterised by annual and resupinate basidiomata with a white pore surface when fresh, a dimitic hyphal system, the presence of dendrohyphidia, broadly ellipsoid to subglobose basidiospores measuring 5-5.8 × 4-5.2 µm. In addition, Crassisporus is a genus in Perenniporia s.l., in which two new combinations Crassisporusminutus and C.mollissimus are proposed. Main morphological characteristics of species related to new taxa are also provided.

Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Risk Factors for Acute Postsurgical Pain: A Narrative Review.

Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.

Efficient tobacco rattle virus-induced gene editing in tomato mediated by the CRISPR/Cas9 system.

Plant virus-based sgRNA delivery strategy has been widely applied for efficient genome editing across various plant species, leveraging its significant advantages in the rapid expression and expansion of sgRNA through virus replication and movement. However, the efficacy of the virus-induced gene editing (VIGE) tool in tomato has yet to be explored. In this paper, we established a TRV-mediated CRISPR/Cas9 genome editing system in the somatic cells of tomato, reporting the validation of VIGE and evaluating the mutagenesis efficiency in both tomato leaves and fruits using high-throughput sequencing. The results demonstrated an approximate 65% efficiency of VIGE in tomato leaves for the selected target genes, with VIGE efficiency reaching up to 50% in tomato fruits. This research not only introduces an efficient tool for reverse genetics but also reveals substantial potential of VIGE in surpassing traditional tissue culture techniques for creating heritable mutations in tomato.