Viral etiology of febrile respiratory syndrome among patients in Liaoning Province, China.

BACKGROUND: Febrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China. METHODS: We tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software. RESULTS: IFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months. CONCLUSIONS: IFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.

SNRPB2 promotes triple-negative breast cancer progression by controlling alternative splicing of MDM4 pre-mRNA.

Alternative splicing generates cancer-specific transcripts and is now recognized as a hallmark of cancer. However, the critical oncogenic spliceosome-related proteins involved in triple-negative breast cancer (TNBC) remain elusive. Here, we explored the expression pattern of spliceosome-related proteins in TNBC, non-TNBC, and normal breast tissues from The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort, revealing higher expression of nearly half of spliceosome-related proteins in TNBC than their counterparts. Among these TNBC-specific spliceosome-related proteins, the expression of SNRPB2 was associated with poor prognosis in patients with TNBC. In TNBC cells, the knockdown of SNRPB2 strongly suppressed cell proliferation and invasion and induced cell cycle arrest. Mechanistically, transcriptome data showed that SNRPB2 knockdown inactivated E2F1 signaling, which regulated the cell cycle. We further validated the downregulation of several cell cycle genes in SNRPB2 knockdown cells. Moreover, the analysis showed that SNRPB2 knockdown triggered the alteration of many alternative splicing events, most of which were skipping of exon. In TNBC cells, it was found that SNRPB2 knockdown led to the skipping of exon 6 in MDM4 pre-mRNA, generating MDM4-S transcript and downregulating MDM4 protein expression. More importantly, downregulation of MDM4 decreased retinoblastoma 1 (Rb1) protein expression, which is a target of MDM4 and a regulator of E2F1 signaling. In summary, the current study revealed an SNRPB2/MDM4/Rb axis in promoting the progression of TNBC, providing novel insights and novel targets for combating TNBC.

Differential effects of polystyrene microplastics on the adsorption of cadmium and ciprofloxacin by tea leaf litter-derived magnetic biochar: Influencing factors and mechanisms.

Water pollution involves the coexistence of microplastics (MPs) and traditional pollutants, and how can MPs influence the adsorption of other pollutants by biochar during the treatment process remains unclear. This study aimed to investigate the influence of polystyrene microplastics (PS MPs) on the adsorption of cadmium (Cd) and ciprofloxacin (CIP) by magnetic biochar (MTBC) in the single and binary systems. MTBC was prepared using tea leaf litter; the effects of time, pH, and salt ions on the adsorption behaviors were investigated; and X-ray photoelectronic spectroscopy (XPS) and density flooding theory analysis were conducted to elucidate the influence mechanisms. Results indicated that PS MPs reduced the pollutants adsorption by MTBC due to the heterogeneous aggregation between PS MPs and MTBC and the surface charge change of MTBC induced by PS MPs. The effects of PS MPs on heavy metals and antibiotics adsorption were distinctly different. PS MPs reduced Cd adsorption on MTBC, which were significantly influenced by the solution pH and salt ions contents, suggesting the participation of electrostatic interaction and ion exchange in the adsorption, whereas the effects of PS MPs on CIP adsorption were inconspicuous. In the hybrid system, PS MPs reduced pollutants adsorption by MTBC with 66.3% decrease for Cd and 12.8% decrease for CIP, and the more remarkable reduction for Cd was due to the predominated physical adsorption, and CIP adsorption was mainly a stable chemisorption. The influence of PS MPs could be resulted from the interaction between PS MPs and MTBC with changing the functional groups and electrostatic potential of MTBC. This study demonstrated that when using biochar to decontaminate wastewater, it is imperative to consider the antagonistic action of MPs, especially for heavy metal removal. PRACTITIONER POINTS: Magnetic biochar (MTBC) was prepared successfully using tea leaf litter. MTBC could be used for cadmium (Cd) and ciprofloxacin (CIP) removal. Polystyrene microplastics (Ps MPs) reduced Cd/CIP adsorption by MTBC. Ps MPs effects on Cd adsorption were more obvious than that of CIP. Ps MPs changed the functional groups and electrostatic potential of MTBC, thus influencing MTBC adsorption.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Solution Synthesis and Light-Emitting Applications of One-Dimensional Lead-Free Cerium(III) Metal Halides.

Combining rare earth elements with the halide perovskite structure offers valuable insights into designing nonlead (Pb) luminescent materials. However, most of these compositions tend to form zero-dimensional (0D) networks of metal-halide polyhedra, with higher-dimensional (1D, 2D, and 3D) structures receiving relatively less exploration. Herein, we present synthesis and optical properties of Cs3CeCl6·3H2O, characterized by its unique 1D crystal structure. The conduction band minimum of Cs3CeCl6·3H2O becomes less localized as a result of the increased structural dimension, making it possible for the materials to achieve an efficient electrical injection. For both Cs3CeCl6·3H2O single crystals and nanocrystals, we also observed remarkable luminescence with near-unity photoluminescence quantum yield and exceptional phase stability. Cs3CeCl6·3H2O single crystals demonstrate an X-ray scintillation light yield of 31900 photons/MeV, higher than that of commercial LuAG:Ce (22000 photons/MeV); electrically driven light-emitting diodes fabricated with Cs3CeCl6·3H2O nanocrystals yield the characteristic emission of Ce3+, indicating their potential use in next-generation violet-light-emitting devices.

π-π conjugated PDI supramolecular regulating the photoluminescence of imine-COFs for sensitive smartphone visual detection of levofloxacin.

As the contamination and enrichment in food chain of levofloxacin (LV) antibiotics have caused a significant threat to life safety, the instant detection of LV has become an urgent need. Here, a PDI-functionalized imine-based covalent organic framework (PDI-COF300) was prepared by the electrostatic self-assembly method as fluorescent probe for smartphone visual detection of LV, which exhibited excellent fluorescence quantum yield (82.68%), greater stability, high sensitivity with detection limit of 0.303 µM. Based on the results of molecular docking and Stern-Volmer equation, the LV detection by PDI-COF300 was mainly a static quenching process through π-π stacked hydrophobic interactions and fluorescence resonance energy transfer. Besides, PDI-COF300 was applied to LV detection in environmental medium and milk samples with recoveries from 85.56% to 108.34% and relative standard deviations <2.70%. This work also provided a new general strategy for using PDI-COF in smartphone devices and fluorescent papers for LV fluorescence detection and microanalysis.

Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer.

The cancer-associated alternative splicing (AS) events generate cancer-related transcripts which are involved in uncontrolled cell proliferation and drug resistance. However, the key AS variants implicated in tamoxifen (TAM) resistance in breast cancer remain elusive. In the current study, we investigated the landscape of AS events in nine pairs of primary and relapse breast tumors from patients receiving TAM-based therapy. We unrevealed a notable association between the inclusion of exon 7.2 in the 5'untranslated region (5'UTR) of ALDOA mRNA and TAM resistance. Mechanistically, the inclusion of ALDOA exon 7.2 enhances the translation efficiency of the transcript, resulting in increased ALDOA protein expression, mTOR pathway activity, and the promotion of TAM resistance in breast cancer cells. Moreover, the inclusion of exon 7.2 in ALDOA mRNA is mediated by MSI1 via direct interaction. In addition, elevated inclusion of ALDOA exon 7.2 or expression of MSI1 is associated with an unfavorable prognosis in patients undergoing endocrine therapy. Notably, treatment with Aldometanib, an ALDOA inhibitor, effectively restrains the growth of TAM-resistant breast cancer cells in vitro and in vivo. The present study unveils the pivotal role of an AS event in ALDOA, under the regulation of MSI1, in driving TAM resistance in breast cancer. Therefore, this study provides a promising therapeutic avenue targeting ALDOA to combat TAM resistance.

Retrograde colon imaging through colonic transendoscopic enteral tubing helps to confirm the cause of difficult colonoscopy: a case report.

Numerous factors can contribute to a difficult colonoscopy, potentially leading to an incomplete procedure and overlooked lesions. Alternative strategies for handling difficult and incomplete colonoscopies should be considered. We present the case of an 85-year-old male who underwent a difficult colonoscopy, during which two expert endoscopists spent 1.5 h attempting various techniques but failed to intubate the cecum. Subsequently, colonic transendoscopic enteral tubing (TET) was performed. Abdominal plain film revealed tortuosity of the TET tube in the left abdomen corresponding to the distribution of the descending colon. Retrograde colon imaging was conducted by injecting a mixture of contrast medium and air into the colon via the TET tube. X-ray demonstrated well-developed visualization of the entire colon and terminal ileum. And evident elongation and tortuosity of the descending colon resembled an N-type folding pattern. The final diagnosis was determined as descending colon redundancy. Colonic TET combined with retrograde colon imaging through the TET tube may serve as an effective supplementary approach for identifying causes of difficult colonoscopy and improving diagnostic accuracy for bowel diseases when complete visualization is not achieved.

Unlocking epigenetics for precision treatment of Ewing's sarcoma.

Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Steering the course of CAR T cell therapy with lipid nanoparticles.

Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.

Modified peroral endoscopic myotomy technique with retrograde on-demand myotomy for achalasia: a retrospective cohort study (with video).

BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.

Risk Factors of New Symptomatic Fractures After Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture.

OBJECTIVE: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, body mass index, bone mineral density (BMD), history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage, and regular antiosteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. Forty-nine levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (adjusted odds ratio [OR]: 6.812, 95% confidence interval {CI}: [1.096, 42.337], P = 0.040), lower BMD (adjusted OR: 0.477, 95% CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (adjusted OR: 16.145, 95% CI: [5.319, 49.005], P = 0.000), and regular antiosteoporosis treatment (adjusted OR: 0.258, 95% CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T-score of lumbar), prior vertebral fractures, and regular antiosteoporosis treatment were independent influencing factors. BMD (T-score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

Utilizing a structure-based virtual screening approach to discover potential LSD1 inhibitors.

BACKGROUND: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment. METHODS: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database. Utilizing virtual docking, we evaluated docking scores and binding modes to identify potential inhibitors. To further validate our findings, we harnessed molecular dynamic simulations and conducted meticulous biochemical experiments to deeply analyze the binding interactions between the protein and compounds. RESULTS: Our results showcased that ZINC10039815 exhibits an exquisite binding mode with LSD1, fitting perfectly into the active pocket and forming robust interactions with multiple critical residues of the protein. CONCLUSIONS: With its significant inhibitory effect on LSD1 activity, ZINC10039815 emerges as a highly promising candidate for the development of novel LSD1 inhibitors.

Full-Scale Model Tests of Two Box-Type Soil-Steel Structures with Different Crown and Haunch Radii.

Compared with circular, arched, and pipe-arched soil-steel structures, box-type soil-steel structures (BTSSSs) have the advantages of high cross-section utilization and low cover depth. However, the degree of influence of the crown and haunch radii on the mechanical performance of BTSSSs is still unclear. Therefore, two full-scale BTSSS models with a span of 6.6 m and a rise of 3.7 m but with different crown and haunch radii were established, and the mechanical properties during backfilling and under live load were tested. Afterward, 2D finite element models (FEMs) were established using the ABAQUS 2020 software and verified using the test data. The influence of cross-section geometric parameters on mechanical performance was analyzed by using the FEM, and a more accurate formula for calculating the bending moment during backfilling was proposed. The results show that the BTSSS with a smaller crown radius has a stronger soil-steel interaction, which promotes more uniform stress on the structure and makes the structure have smaller relative deformations, bending moments, and earth pressure. The span and arch height greatly influence the bending moment and deformation of the structure. Based on the CHBDC, the crown and haunch radii were included in the revised calculation formula.

Vacancy Engineering in 2D Transition Metal Chalcogenide Photocatalyst: Structure Modulation, Function and Synergy Application.

Transition metal chalcogenides (TMCs) are widely used in photocatalytic fields such as hydrogen evolution, nitrogen fixation, and pollutant degradation due to their suitable bandgaps, tunable electronic and optical properties, and strong reducing ability. The unique 2D malleability structure provides a pre-designed platform for customizable structures. The introduction of vacancy engineering makes up for the shortcomings of photocorrosion and limited light response and provides the greatest support for TMCs in terms of kinetics and thermodynamics in photocatalysis. This work reviews the effect of vacancy engineering on photocatalytic performance based on 2D semiconductor TMCs. The characteristics of vacancy introduction strategies are summarized, and the development of photocatalysis of vacancy engineering TMCs materials in energy conversion, degradation, and biological applications is reviewed. The contribution of vacancies in the optical range and charge transfer kinetics is also discussed from the perspective of structure manipulation. Vacancy engineering not only controls and optimizes the structure of the TMCs, but also improves the optical properties, charge transfer, and surface properties. The synergies between TMCs vacancy engineering and atomic doping, other vacancies, and heterojunction composite techniques are discussed in detail, followed by a summary of current trends and potential for expansion.

Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease.

Gastric peroral endoscopic myotomy (G-POME) is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tunnel around the pyloric sphincter. In 2013, Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy, providing a new direction for the treatment of gastroparesis. With the recent and rapid development of G-POME therapy technology, progress has been made in the treatment of gastroparesis and other upper digestive tract diseases, such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture, with G-POME. This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

Advances in molecular mechanisms of inflammatory bowel disease­associated colorectal cancer (Review).

The link between inflammation and cancer is well documented and colonic inflammation caused by inflammatory bowel disease (IBD) is thought to be a high-risk factor for the development of colorectal cancer (CRC). The complex crosstalk between epithelial and inflammatory cells is thought to underlie the progression from inflammation to cancer. The present review collates and summarises recent advances in the understanding of the pathogenesis of IBD-associated CRC (IBD-CRC), including the oncogenic mechanisms of the main inflammatory signalling pathways and genetic alterations induced by oxidative stress during colonic inflammation, and discusses the crosstalk between the tumour microenvironment, intestinal flora and host immune factors during inflammatory oncogenesis in colitis-associated CRC. In addition, the therapeutic implications of anti-inflammatory therapy for IBD-CRC were discussed, intending to provide new insight into improve clinical practice.

Natural hyperoside extracted from hawthorn exhibits antiviral activity against porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.