Search

Abstract Background Disease progression within 24 months (POD24) significantly impacts overall survival (OS) in patients with follicular lymphoma (FL). This study aimed to develop a robust predictive model, FLIPI-C, using a machine learning approach to identify FL patients at high risk of POD24. Methods A cohort of 1,938 FL patients (FL1-3a) from seventeen centers nationwide in China was randomly divided into training and internal validation sets (2:1 ratio). XGBoost was utilized to construct the POD24-predicting model, which was internally validated in the validation set and externally validated in the GALLIUM cohort. Key predictors of POD24 included lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) > ULN, low hemoglobin (Hb), elevated beta-2 microglobulin (β2-MG), maximum standardized uptake value (SUVmax), and lymph node involvement. The FLIPI-C model assigned 2 points to LMR and 1 point to each of the other variables. Results The FLIPI-C model demonstrated superior accuracy (AUC) for predicting POD24 and 3-year overall survival (OS) in both the internal (AUC POD24: 0.764, OS: 0.700) and external validation cohorts (AUC POD24: 0.703, OS: 0.653), compared to existing models (FLIPI, FLIPI-2, PRIMA-PI, FLEX). Decision curve analysis confirmed the superior net benefits of FLIPI-C. Conclusions Developed using a machine learning approach, the FLIPI-C model offers superior predictive accuracy and utilizes simple, widely available markers. It holds promise for informing treatment decisions and prognostic assessments in clinical practice for FL patients at high risk of POD24.

Abstract Background A tyrosine kinase inhibitor (TKI) such as Imatinib (IM) is the preferred treatment for Chronic Myeloid Leukemia (CML). However, the emergence of IM resistance presents a significant challenge to disease management. A characteristic of cancer cells, including IM-resistant CMLs, are characterized by heightened uptake of glucose and aberrant glycolysis in the cytosol, which is known as the Warburg effect. In addition to its potential to modulate the Warburg effect, Chiglitazar (Chi), a compound that regulates glucose metabolism, has also been investigated for its implication in cancer treatment. This suggests that combining Chi with IM may be a therapeutic strategy for overcoming IM resistance in CML. Methods Sensitive and IM-resistance CML cells were treated with Chi in vitro, followed by detecting of extracellular acidification rate (ECAR) using a Seahorse XF Analyzer. CML cell proliferation, cell cycle distribution, and apoptosis were tested by CCK-8 assay and flow cytometry. RNA sequencing was utilized to investigate potential transcriptional changes induced by Chi usage. In vivo studies were conducted on immunodeficient mice implanted with CML cells and given Chi and/or IM later. Tumor growth was monitored, as well as tumor burden and survival rates between groups. Results Our metabonomic, transcriptomic, and molecular biology studies demonstrated that Chi, in part, diminished the Warburg effect by reducing glucose and lactate production in imatinib-resistant CML cells through the PPARγ/mTOR/PKM2 pathway. This modulation of glucose metabolism resulted in reduced cell proliferation and enhanced sensitivity to IM in imatinib-resistant CML cells in vitro. Rescue assay by introducing shPPARγ or mTOR activator verified the underlying regulatory pathway. Also, the combination of Chi and IM synergistically increased the sensitivity of IM in vivo and prolonged the survival of imatinib-resistance CML transplanted mice. Conclusions Our results demonstrated the potential of Chi to overcome IM resistance in vitro and in vivo. By inhibiting the Warburg effect through the PPARγ/mTOR/PKM2 pathway, Chi resensitizes CML cells towards imatinib treatment. Combining IM with Chi is an alternative therapeutic option for CML management, especially for IM-resistant CML patients.

Abstract Background In recent years, the concept of precision medicine has gradually permeated the field of nursing, presenting new challenges for neurosurgical nursing staff. Traditional teaching methods often struggle to adequately convey complex anatomical knowledge and nursing skills, thereby affecting the learning outcomes and clinical decision-making abilities of nurses. As an innovative educational tool, three-dimensional (3D) printing technology has demonstrated significant potential in medical education in recent years. Therefore, this project aims to explore the advantages and feasibility of using 3D printed models as a novel teaching tool in neurosurgical nursing. Methods The study involved 80 nursing personnel who participated in the neurosurgical rotation training at Shaoxing People’s Hospital from 2022 to 2023. The control group (40 individuals) used only traditional teaching tools such as textbooks, multimedia courseware, and laboratory equipment for theoretical and practical training based on the curriculum. The experimental group (40 individuals) incorporated a 3D printing model database as an innovative teaching tool on the basis of traditional teaching methods, and used patient-specific 3D printed models for precise nursing training. After the training, both groups were assessed for theoretical and practical abilities, professional values, job satisfaction, and the prognosis of intracranial aneurysm patients they cared for. Results The experimental group demonstrated superior scores in theoretical and practical abilities, professional values, and job satisfaction compared to the control group. During the training period, patients with intracranial aneurysms receiving precision nursing care from the experimental group showed better quality of life and neurological functional outcomes compared to the control group. Conclusions The nursing training system based on 3D printing models can enhance the learning efficiency and nursing work satisfaction of nursing personnel. It may have a positive impact on the professional values of nursing personnel, thereby laying a solid foundation for providing high-quality, precise nursing services in the field of neurosurgery in the future.

Abstract Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2–4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (

Abstract Bacterial biofilms, often forming on medical devices, can lead to treatment failure due to their increased antimicrobial resistance. Cefepime-avibactam (CFP-AVI) exhibits potent activities against Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) when used with polymyxin B (PMB). However, its efficacy in biofilm-related infections is unknown. The present study aimed to evaluate the activity of PMB combined with CFP-AVI against the biofilms of PMB-resistant Gram-negative bacteria. Five K. pneumoniae strains and three P. aeruginosa strains known to be PMB-resistant and prone to biofilm formation were selected and evaluated. Antimicrobial susceptibility assays demonstrated that the minimal biofilm inhibitory and eradication concentrations of PMB and CFP-AVI for biofilms formed by the eight strains were significantly higher than the minimal inhibitory concentrations of the antibiotics for planktonic cells. The biofilm formation inhibition and eradication assays showed that PMB combined with CFP-AVI cannot only suppress the formation of biofilm but also effectively eradicate the preformed mature biofilms. In a modified in vitro pharmacokinetic/pharmacodynamic biofilm model, CFP-AVI monotherapy exhibited a bacteriostatic or effective activity against the biofilms of seven strains, whereas PMB monotherapy did not have any activity at 72 h. However, PMB combined with CFP-AVI demonstrated bactericidal activity against the biofilms of all strains at 72 h. In an in vivo Galleria mellonella infection model, the 7-day survival rates of larvae infected with biofilm implants of K. pneumoniae or P. aeruginosa were 0-6.7%, 40.0-63.3%, and 46.7–90.0%, respectively, for PMB alone, CFP-AVI alone, and PMB combined with CFP-AVI; the combination therapy increased the rate by 6.7–33.3% (P

Abstract Background Postoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB). Methods Sixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively. Results Two patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB. Conclusions PN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB. Trial registration This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021).

Abstract High-end equipment always operate in low-speed and heavy-load working environments, highlighting the need for cam-lobe hydraulic motors with excellent speed stability (< 1 r/min) and ultrahigh-power rotary output (> 1 MW). The successful operation of cam-lobe hydraulic motors relies on the circulation supply of high- and low-pressure oil. However, the switching between high-/low-pressure oil controlled by the oil distributor inevitably causes an obvious pressure impact and speed pulsation, which directly reduces the speed stability of hydraulic motors. Therefore, an optimization design approach for the oil distributor port is proposed to minimize the speed pulsation of cam-lobe hydraulic motors. In the proposed approach, a simulation model that links the oil distributor port structural parameters with the hydraulic motor speed pulsation was developed to clarify the effect of the oil distributor structural parameters on speed pulsation. Then, an orthogonal analysis method was used to identify the optimized oil distributor port structural parameters while minimizing the hydraulic motor’s speed pulsation as much as possible. Finally, several experiments were conducted to validate the effectiveness and accuracy of the proposed optimization design approach. The experimental results indicate that the pulsation rate of the hydraulic motor equipped with the optimized oil distributor was 62.5% lower than that of the original motor at a working pressure of 25 MPa, which is consistent with the simulation results using the proposed optimization design approach. The findings of this study offer a feasible and effective approach to guide the design optimization of the oil distributor port for low-pulsation hydraulic motors.

Abstract The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee.

Abstract Hydraulic actuated quadruped robots have bright application prospects and significant research values in unmanned area investigation, disaster rescue and other scenarios, due to the advantages of high payload and high power to weight ratio. Among these fields, inevitable collision of robots may occur when contact with unknown objects, step on empty objects, or collapse, all of which have an impact on the working hydraulic system. To overcome the unknown external disturbances, this paper proposes an active disturbance rejection control (ADRC) strategy of double vane hydraulic rotary actuators for the hip joints of the quadruped robots. Considering the order of the valve-controlled actuator model, a three-stage tracking differentiator, a four-stage extended state observer, and a state error feedback controller are designed relatively, and the extended state observer is adopted to observe and compensate the uncertainty of external load torque of the system. The effectiveness of the ADRC method is verified in simulation environment and a single joint experimental platform. Moreover, the impact experiments of the limb leg unit are carried out after introducing the proposed ADRC strategy into hip joint, the limb leg unit of quadruped robots presents better impact resistance ability.

Abstract In the realm of reservoir development, the optimization of well placement constitutes a cornerstone challenge with significant implications that directly determine the recovery rate and economic benefits of oil and gas production. This research proposes a novel approach to optimizing well placement in reservoirs by integrating reservoir numerical simulations with intelligent optimization algorithms. The quintessence of this inquiry revolves around the strategic placing of wells amidst the complex geological fabric of reservoirs, where the objective function landscape often manifests with non-smooth, multimodal characteristics. To address those issues, the Weighted Mapping of Productivity Potential (WMPP) technique, fortified by the Simulated Annealing algorithm to judiciously ascertain specific weighting coefficients for the computation of WMPP across reservoirs is introduced in this study. Furthermore, an emblematic carbonate reservoir model serves to corroborate the adaptability and viability of WMPP for well placement optimization, underscoring its efficacy as a swift, economically viable instrument for the delineation of prospective reservoir zones and the guidance of drilling initiatives. The optimization results show that the well placement scheme guided by WMPP, which required 7 fewer wells than the oil initially in place (OOIP)-based scheme, improved 21.74% oil production over the twenty years production period. This comprehensive workflow proffers invaluable insights and benchmarks for the formulation of well placement strategies, with the proposed methodology, in its apparent simplicity, showcasing remarkable efficiency.

Abstract Cam-lobe radial-piston hydraulic motors are widely used as rotation driving units for various marine machinery owing to their ultrahigh output torque (more than 100 kN m). A multi-row cam roller bearing (MCRB) is the key component that directly determines the fatigue life of a cam-lobe radial-piston hydraulic motor. However, compact geometry and complex loads render MCRB susceptible to fatigue failure, highlighting the need for an optimized MCRB to achieve longer fatigue life and higher reliability. Therefore, this study proposes an innovative geometry optimization method for an MCRB to improve its fatigue life. In this method, a quasi-static model was developed to calculate the load distribution, with the fatigue life of the MCRB calculated using both basic dynamic loading and load distribution. Subsequently, a genetic algorithm was used to obtain the optimized geometry parameters, which significantly improved the fatigue life of the MCRB. Finally, a loading test was conducted on a hydraulic motor installed with both the initial and optimized MCRB to validate the effectiveness of the proposed optimization method. This study provides a theoretical guideline for optimizing the design of MCRB, thereby increasing the fatigue life of hydraulic motors.

To advance the circular economy (CE), it is crucial to gain insights into the evolution of public attention, cognitive pathways related to circular products, and key public concerns. To achieve these objectives, we collected data from diverse platforms, including Twitter, Reddit, and The Guardian, and utilised three topic models to analyse the data. Given the performance of topic modelling may vary depending on hyperparameter settings, we proposed a novel framework that integrates twin (single- and multi-objective) hyperparameter optimisation for CE analysis. Systematic experiments were conducted to determine appropriate hyperparameters under different constraints, providing valuable insights into the correlations between CE and public attention. Our findings reveal that economic implications of sustainability and circular practices, particularly around recyclable materials and environmentally sustainable technologies, remain a significant public concern. Topics related to sustainable development and environmental protection technologies are particularly prominent on The Guardian, while Twitter discussions are comparatively sparse. These insights highlight the importance of targeted education programmes, business incentives adopt CE practices, and stringent waste management policies alongside improved recycling processes.

Background: Macular hole (MH) formation after rhegmatogenous retinal detachment (RRD) surgery is rare, and in most cases, additional surgical procedures are required to repair MH. Spontaneous closure of the MH is even rarer. In this study, we aimed to report a series of cases of spontaneous closure of the secondary MH and provide a review of the literature. Methods: We retrospectively collected the cases of secondary MH formation following vitrectomy in RRD patients followed by spontaneous closure. Ophthalmological data at presentation and during follow-up were collected and analyzed. Results: We reported a total of three RRD patients aged 31,67,12 years, including two females and one male. The three patients underwent pars plana vitrectomy (PPV) with either silicone oil tamponade or air tamponade. Optical coherence tomography (OCT) revealed a second full-thickness MH formation with remnant vitreous cortex bridging in the macular region during early follow-up. Observations of the cases revealed subsequent remnant vitreous cortex traction remission and spontaneous closure of MH during follow-up, although with subsequent thin macular and abnormal macular structure. Conclusion: The progression of secondary MH formation in the cases may be related to vitreomacular traction (VMT) by the posterior vitreous cortex remnant after PPV, and the release of VMT may help the spontaneous closure of the MH after PPV for RRD.

Objective This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis.Methods 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis.Results The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p

Nanoarchitectonics, as a technology to arrange nano-sized structural units such as molecules in a desired configuration, requires nano-organization, which usually relies on intermolecular interactions. This review briefly introduces the development of using enzymatic reactions to control intermolecular interactions for generating artificial nanoarchitectures in a cellular environment. We begin the discussion with the early examples and uniqueness of enzymatically controlled self-assembly. Then, we describe examples of generating intracellular nanostructures and their relevant applications. Subsequently, we discuss cases of forming nanostructures on the cell surface via enzymatic reactions. Following that, we highlight the use of enzymatic reactions for creating intercellular nanostructures. Finally, we provide a summary and outlook on the promises and future direction of this strategy. Our aim is to give an updated introduction to the use of enzymatic reaction in regulating intermolecular interactions, a phenomenon ubiquitous in biology but relatively less explored by chemists and materials scientists. Our goal is to stimulate new developments in this simple and versatile approach for addressing societal needs.

Background The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.Methods The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables.Results Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression.Conclusions These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1+ T cells, higher average nearest neighbor distance between T cells and PAX5+ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1+ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.

Background Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis.Objective This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients.Methods Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group).Results Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p

Magnetic Resonance Imaging (MRI) is a globally acknowledged diagnostic procedure particularly recognized for its superior soft tissue contrast, high-resolution imaging, and non-ionizing radiation properties, making it an indispensable tool in the medical field. However, to optimize MRI’s sensitivity and specificity towards certain diseases, use of contrast agents becomes necessary. Recent developments focus on nanomaterial-based MRI contrast agents to improve diagnostic accuracy and image quality. This review highlights advancements in such agents, including metal oxide nanoparticles, carbon-based materials, gold nanoparticles, and quantum dots. It discusses their roles in MRI-guided therapies like targeted drug delivery, hyperthermia, radiation therapy, photodynamic therapy, immunity-boosting therapy, and gene therapy. Insights into the future potential of MRI contrast agents in imaging medicine are also provided.

Chronic otitis media with effusion (COME) is a common cause of hearing loss in children and adults. Laryngopharyngeal reflux (LPR) is often overlooked in the clinical management of COME complicated by LPR. This study aimed to investigate the presence and concentration of trypsin and pepsin in the middle ear effusion (MEE), as well as the recurrence rate of otitis media with effusion (OME) in COME patients with trypsin-/pepsin-positive MEE after acid-suppressive treatment (AST). In this study, trypsin and pepsin were found in the MEE of COME patients. Follow-up results showed that the recurrence rate of OME within 1 year was significantly lower in the AST group than in the non-AST group. Taken together, patients with COME can be offered pepsin detection of MEE, and if the pepsin test is positive, acid-suppressing drugs such as proton pump inhibitors could be recommended to prevent the recurrence of OME.

BackgroundWith a growing global population affected by Chronic Obstructive Pulmonary Disease (COPD), the traditional Chinese herbal formula Houpo Mahuang Decoction (HPMHD) has been used for centuries to address respiratory ailments. While studies have demonstrated the therapeutic benefits of HPMHD in COPD, the effective active ingredients, potential targets, and molecular mechanisms underlying its effectiveness remained unclear.MethodsThe mechanisms of action of certain HPMHD components, targets, and pathways for the treatment of COPD were predicted using a network pharmacology method. We induced a COPD mouse model using porcine pancreatic elastase and evaluated the pathological changes and healing processes through HE and Masson staining. Immunofluorescence was used to assess the levels of IL-6 and TNF-ɑ. RNA-Seq analysis was conducted to identify differentially expressed genes (DEGs) in the lungs of normal, control, and treated mice, revealing the biological pathways enriched by HPMHD in COPD treatment. Finally, the expression of DEGs was verified using Western blotting and RT-qPCR.ResultsHPMHD effectively alleviated pathological symptoms and improved COPD in mice by modulating the IL-17 signaling pathway. Treatment with HPMHD improved lung morphology and structure, reduced inflammatory cell infiltration, and inhibited IL-6 and TNF-ɑ levels. Network pharmacology and transcriptomics further revealed the mechanism, indicating that the IL-17 signaling pathway might been instrumental in the inhibitory effect of HPMHD on mouse model of COPD. Subsequent experiments, including protein blotting and RT-qPCR analysis, confirmed the activation of the IL-17 signaling pathway by HPMHD in the COPD mouse model, further supporting the initial findings.ConclusionHPMHD was shown to alleviate COPD and reduce lung inflammation in mice, potentially through the activation of the IL-17 signaling pathway. This study provides a novel direction for the development of COPD drugs.

Hyperuricemia (HUA) is a vital risk factor for chronic kidney diseases (CKD) and development of functional foods capable of protecting CKD is of importance. This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides (ADBP) on HUA-induced kidney damage. In the present study, we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents. In vitro results found that ADBP protected uric acid (UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense. In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice, evidenced by a remarkable decrease in serum UA, creatinine and blood urea nitrogen, improving kidney UA excretion, antioxidant defense and histological kidney deterioration. Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction. Intriguingly, ADBP restored the gut microbiome homeostasis in CKD mice, especially with respect to the elevated helpful microbial abundance, and the decreased harmful bacterial abundance. This study demonstrated that ADBP displayed great nephroprotective effects, and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Abstract Objective The aim of this study is to examine the impact of a nursing intervention based on stress system theory, coupled with painting therapy, on children experiencing post-traumatic stress disorder (PTSD) subsequent to an accidental injury. Methods The clinical data of 100 children diagnosed with PTSD following accidental injuries were retrospectively analyzed for the period spanning April 2021 to May 2023. There were 48 children who received standard nursing care between April 2021 and April 2022 in the control group, and 52 children who received nursing intervention based on stress system theory combined with painting therapy between May 2022 and May 2023 in the observation group. Scores of PTSD Self-evaluation Scale (PTSD-SS), post-traumatic growth, coping style, quality of life, and family satisfaction were compared between the two groups. Results Prior to nursing care, the scores of each dimension in the PTSD-SS, post-traumatic growth, coping style, and quality of life were similar between the two groups (P > 0.05). Following nursing intervention, the observation group exhibited lower scores in each dimension of the PTSD-SS compared to the control group. Moreover, the scores in each dimension of the children’s version of the Post-Traumatic Growth Inventory (PTGI) were higher in the observation group than in the control group. Additionally, the Confrontation scores in the Medical Coping Modes Questionnaire (MCMQ) were higher in the observation group than in the control group, while the scores of Avoidance and Resignation were lower in the observation group than in the control group. The scores of each dimension in the Pediatric Quality of Life Inventory Measurement Models (PedsQL4.0) were higher than those in the control group (P

Laser cladding is an advanced surface engineering technology capable of producing Ni-based coatings with high wear resistance. Incorporating graphene (Gr) into Ni-based coatings has great potential for improving the tribological properties of component surface. To date, the effects of Ni-decorated Gr (Ni@Gr) content on the tribological properties of Ni@Gr/Ni-based composite coatings and their surface wear mechanism have yet to be fully understood. In this study, Ni@Gr/Ni-based composite coatings with varying Ni@Gr contents (0, 2, 4, and 6 wt%) were prepared by laser cladding, and the effects of different Ni@Gr contents on the microstructure and tribological properties were investigated in detail. The results showed that the incorporation of Ni@Gr resulted in significant grain refinement and enhanced dislocations, along with an increase in carbide content. The smallest grain size (2.88 μm) and highest hardness (1039.3 HV0.2) were observed in the Ni@Gr/Ni-based composite coating with 4 wt% Ni@Gr. Simultaneously, the coefficient of the friction (COF) and the wear volume of the coating reach the minimum values of 0.3221 and 2.0123 × 10−2 mm−3, representing a 15.44% and 36.29% reduction compared to the pure Ni-based alloy coating, respectively. Based on the observed results, the wear mechanism of Ni@Gr/Ni-based composite coatings was analyzed and revealed. The high wear resistance of the coating is attributed to the optimal mechanical properties resulting from grain refinement and dislocation strengthening, as well as the uniformly distributed Ni@Gr with easily sheared layered structures that generate a lubricating film, effectively reducing the contact area between the coating and the grinding ball while resisting friction loads. This study could provide a deep understanding of the wear mechanism of Gr-doped surface coatings, contributing to the advancement of this field.

AlCoCrFeMo0.05Ni2 high-entropy alloy (HEA) has great potential for high-temperature applications. However, its FCC matrix will decompose during annealing, which seriously limits its high-temperature applications. Here, the lattice distortion, Gibbs free energy change, phonon spectra, density of states, and bond length distribution of the FCC matrix were calculated by first-principles calculations. The findings indicate that the primary barrier to the formation of a single homogeneous solid solution in the alloy is more closely associated with Gibbs free energy rather than the degree of lattice distortion. The vibration frequency of Al is not in sync with the overall structure, making it prone to desolvation at elevated temperatures. Furthermore, an analysis of bond lengths reveals that the Al–Ni bond length is significantly shorter than the theoretical value, facilitating the formation of a (Ni, Al)-rich phase. In contrast, the longer bond lengths of Al–Cr and Al–Mo facilitate the detachment of Cr and Mo from the (Ni, Al)-rich phase, resulting in the formation of (Cr, Mo)-rich phase. This in-depth investigation sheds light on the phase decomposition mechanism of high-entropy alloys, offering valuable insights for future research in this field.

Abstract In this work, we test the cosmic distance duality relation (CDDR) by comparing the angular diameter distance (ADD) derived from the transverse Baryon Acoustic Oscillations (BAO) data with the luminosity distance (LD) from the Pantheon type Ia supernova (SNIa) sample. The binning method and Gaussian process are employed to match ADD data with LD data at the same redshift. First, we use nonparametric and parametric methods to investigate the impact of the specific prior values of the absolute magnitude $$M_\textrm{B}$$ M B from SNIa observations and the sound horizon scale $$r_\textrm{s}$$ r s from transverse BAO measurements on the CDDR tests. The results obtained from the parametric and non-parametric methods indicate that specific prior values of $$M_\textrm{B}$$ M B and $$r_\textrm{s}$$ r s lead to significant biases on the CDDR test. Then, to avoid these biases, we propose a method independent of $$M_\textrm{B}$$ M B and $$r_\textrm{s}$$ r s to test CDDR by considering the fiducial value of $$\kappa \equiv 10^{M_\textrm{B} \over 5}r_\textrm{s}$$ κ ≡ 10 M B 5 r s as a nuisance parameter and then marginalizing its influence with a flat prior in the analysis. No violation of the CDDR is found, and the transverse BAO measurement can be used as a powerful tool to verify the validity of CDDR in the cosmological-model-independent method.

Abstract Background The treatment of myeloid sarcoma (MS) is challenging and has not markedly improved patient prognosis. The introduction of venetoclax (VEN) has changed the treatment of MS, and venetoclax-based therapy has been described as very promising in several case reports. Methods In this retrospective study, we analyzed the treatment outcomes of 14 patients with MS treated with venetoclax-based therapy at The First Affiliated Hospital of Xiamen University from January 2020 to October 2023 Results The cohort consisted of 7 (50%) women and 7 (50%) men with an average age of 37.5 years. Four patients (28.6%) had isolated MS de novo, 2 (14.2%) were diagnosed synchronously with AML, and 8 (57.2%) had isolated extramedullary relapse. The most common sites for MS in our cohort were the skin and lung, followed by the spinal canal, soft tissue, bone and kidney. Five patients were affected at more than three sites. Nine patients received VEN in combination with azacytidine, and 5 patients received VEN in combination with other agents. The median number of venetoclax therapies administered was 2 cycles (range: 1–10 cycles). A response was observed in all patients included in the study, with 8 patients (57.2%) achieving a CR and 3 patients (21.4%) achieving a PR, corresponding to an ORR (including CR and PR) of 78.6%. The median follow-up time for all patients was 13 months (range 1–44 months), and the 1 year OS for all patients was 67.7%. Conclusions Venetoclax-based therapy shows excellent efficacy and safety in MS patients in the “real world” at a single institution, and a corresponding prospective study is needed to verify this conclusion.

Heterogeneous asymmetric catalysis is an important strategy for the industrial production of chiral compounds. Herein, we reported a polymer-bound Xu-Phos-derived palladium catalyst that shows good performance in heterogeneous asymmetric reductive Heck reaction of allyl aryl ethers. This heterogeneous catalyst was easily prepared by efficient immobilization of the sulfonamide phosphine ligand (Xu-Phos) in the cross-linked polystyrene via copolymerization, and exhibits similar catalytic activity and enantioselectivity to that of the homogeneous catalyst. Moreover, the heterogeneous catalyst system is proved to be easily recovered and reused several times without losing catalytic activity obviously.

Abstract Fixation and functionalisation of N2 by main-group elements has remained scarce. Herein, we report a fixation and cleavage of the N ≡ N triple bond achieved in a dinitrogen (N2) matrix by the reaction of hydrogen and laser-ablated silicon atoms. The four-membered heterocycle H2Si(μ-N)2SiH2, the H2SiNN(H2) and HNSiNH complexes are characterized by infrared spectroscopy in conjunction with quantum-chemical calculations. The synergistic interaction of the two SiH2 moieties with N2 results in the formation of final product H2Si(μ-N)2SiH2, and theoretical calculations reveal the donation of electron density of Si to π* antibonding orbitals and the removal of electron density from the π bonding orbitals of N2, leading to cleave the non-polar and strong NN triple bond.

High-energy shot peening (HESP) is an effective way to achieve surface nanocrystallization modification of additive manufactured metal parts, significantly improving their mechanical properties. Yet, there is still a lack of deep understanding of the surface nanocrystallization evolution mechanism of additive manufactured metals. For that, this study focuses on the surface nanocrystallization mechanism of selective laser melted 316L stainless steel treated by HESP treatment. The detailed microstructural characteristics are investigated via optical microscope (OM) and transmission electron microscopy (TEM). The experimental results show that the matrix layer, the low-strain matrix layer, the elongated ultrafine grain layer, the short rod-like ultrafine grain layer, and the equiaxed nanograin layer occurred in sequence from the matrix to the topmost surface. HESP treatment enables the gradient grain refinement from the matrix with a micrometer structure of about 120 mm to the topmost surface with an average grain size of about 25 nm. The evolution of surface nanocrystallization has resulted from the interaction of high-density dislocation, dislocation tangles (DTS), and twins. This study could provide a deep understanding of the surface nanocrystallization evolution mechanism of additive manufactured metal parts treated by HESP.

Abstract Relative permeability (RP) curves which provide fundamental insights into porous media flow behavior serve as critical parameters in reservoir engineering and numerical simulation studies. However, obtaining accurate RP curves remains a challenge due to expensive experimental costs, core contamination, measurement errors, and other factors. To address this issue, an innovative approach using deep learning strategy is proposed for the prediction of rock sample RP curves directly from mercury injection capillary pressure (MICP) measurements which include the mercury injection curve, mercury withdrawal curve, and pore size distribution. To capture the distinct characteristics of different rock samples' MICP curves effectively, the Gramian Angular Field (GAF) based graph transformation method is introduced for mapping the curves into richly informative image forms. Subsequently, these 2D images are combined into three-channel red, green, blue (RGB) images and fed into a Convolutional Long Short-Term Memory (ConvLSTM) model within our established self-supervised learning framework. Simultaneously the dependencies and evolutionary sequences among image samples are captured through the limited MICP-RP samples and self-supervised learning framework. After that, a highly generalized RP curve calculation proxy framework based on deep learning called RPCDL is constructed by the autonomously generated nearly infinite training samples. The remarkable performance of the proposed method is verified with the experimental data from rock samples in the X oilfield. When applied to 37 small-sample data spaces for the prediction of 10 test samples, the average relative error is 3.6%, which demonstrates the effectiveness of our approach in mapping MICP experimental results to corresponding RP curves. Moreover, the comparison study against traditional CNN and LSTM illustrated the great performance of the RPCDL method in the prediction of both S o and S w lines in oil–water RP curves. To this end, this method offers an intelligent and robust means for efficiently estimating RP curves in various reservoir engineering scenarios without costly experiments.

Merging traditional Chinese medicine's (TCM) principles of medicine-food homology with modern flavor chemistry, this research unveils PungentDB (http://www.pungentdb.org.cn/home), a database documenting 205 unique pungent flavor compounds from 231 TCMs. It provides detailed insights into their chemical attributes, biological targets (including IC50/EC50 values), and molecular structures (2D/3D), enriched with visualizations of target organ distribution and protein structures, exploring the pungent flavor space with the help of a feature-rich visual interface. This collection, derived from over 3249 sources and highlighting 9129 targets, delves into the compounds' unique pungent flavors—taste, aroma, and thermal sensations—and their interaction with taste and olfactory receptors. PungentDB bridges ancient wisdom and culinary innovation, offering a nuanced exploration of pungent flavors' role in enhancing food quality, safety, and sensory experiences. This initiative propels flavor chemistry forward, serving as a pivotal resource for food science advancement and the innovative application of pungent flavors.

Objective: This study evaluates the AI-assisted diagnostic potential of computed tomography (CT) for bone cancer and its influence on patient care during the pre- and post-treatment phases. It compares patient management approaches based on CT severity levels and identifies distinct CT phenotypes linked to disease severity. Methodology: We retrospectively examined 50 patients diagnosed with bone cancer between December 2022 and June 2023. The CT scans were analyzed according to the Radiological Society of North America (RSNA) guidelines. This study was performed using the deep convolutional neutral network (DCNN) model to assist doctors in diagnosing bone tumors through CT scanning. Patients’ management approaches were compared based on the severity levels indicated by CT scans. Results: Fifty patients participated in this study, with a median age of 67.2 years, ranging from 32 to 89 years. Of them, 38 % were female and 62 % were male. In 2022, 19 individuals (13 males and 6 females, ages 32 to 84) were assessed, with a mean age of 59.9 years. In 2023, 31 individuals, aged 54 to 89 with a mean age of 71.6 years, were assessed; among them were 18 men and 13 women. SPECT scans revealed the following key diagnostic features: 85.9 % of patients exhibited bone lesions with ground-glass opacities, 88 % had multipolar involvement, 92.8 % had bilateral involvement, and 92.8 % showed peripheral involvement. The severity scores based on CT scans were significantly higher in patients requiring intensive care, with scores above 14 being more common in this group. Conclusion: Distinct CT findings during the AI-assisted diagnosis and treatment of bone cancer provided prompt and sensitive examination capabilities. Notably, two CT phenotypes emerged, associated with large consolidation patterns and high severity scores, offering crucial insights into disease severity and aiding in clinical decision-making for intensive care requirements. The study underscores the importance of CT in the effective monitoring and management of bone cancer pre- and post-treatment.

Background: Tumor genomic profiling has a significant impact on the selection of targeted therapy. Circulating tumor DNA (ctDNA) has emerged as a noninvasive, and reproducible assay compared with tissue biopsy. We aimed to evaluate its utility in identifying mutations and guiding targeted therapy for lung cancer. Methods: A total of 173 lung cancer patients underwent next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. The performance of the ctDNA NGS assay in identifying genetic mutations or alterations was compared with tissue biopsy and droplet digital PCR (ddPCR). The treatment response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapies based on the ctDNA assay results was also assessed. Results: The ctDNA was detected in 61.85% of patients. Tissue mutations were detected in paired ctDNA in 38.57% of cases, while ctDNA mutations were detected in paired tissues in 89.1% of cases. The ctDNA increased the number of advanced non-small cell lung cancer (NSCLC) patients who received NCCN-recommended genetic testing by 12%. The concordance between ddPCR and ctDNA was relatively high reaching 99.43%. EGFR T790M/C797S c.G2390C and EGFR T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the EGFR T790M mutation, which was missed by tissue biopsy in patient 01149, who developed drug resistance after 1 year of EGFR-TKI therapy. Of the 17 patients who received EGFR-TKI targeted therapies based on the ctDNA NGS results, 12 patients achieved a partial response and two patients had stable disease. Conclusions: The results demonstrated that the ctDNA assay could partially overcome tumor heterogeneity in detecting mutations and provide complementary information on tumor genomic profiles. Moreover, the presence of EGFR mutations in ctDNA could offer valuable guidance for selecting appropriate EGFR-TKI treatment for advanced lung cancer patients. However, it is important to note that the ctDNA NGS assay has certain limitations in fully identifying all genomic alterations present in the tumor.

Background In patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens.Methods In a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes.Results Of the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity.Conclusions Zuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL.Trial registration number Chinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.

Abstract Carbopalladation‐initiated cascade reaction involving 1,4‐Pd migration is a straightforward and powerful approach to activate remote C─H bond, forging versatile fused polycyclic compounds containing fluorene fragment which are highly valuable synthetic targets. However, its asymmetric variants pose considerable challenges and have not been explored. Here the first asymmetric palladium‐catalyzed tandem carbopalladation is reported, 1,4‐Pd migration reaction of ortho‐iodophenol‐derived allyl ether under mild conditions, allowing the transformation of a wide range of substrates in good to excellent enantioselectivities, and providing a facile and straight forward access to tetracyclic dihydroindeno[1,2,3‐de]chromene bearing a chiral fluorene skeleton. A good functional group tolerance, high stereoselectivity, as well as the good chiroptical properties (high fluorescence quantum yields, circular dichroism) of the products make this approach highly attractive. Moreover, density functional theory (DFT) calculations indicate that the protonation of five‐membered palladacycle intermediate is more favorable rather than its direct reductive elimination process.

Cam-lobe radial-piston hydraulic motors are widely used in large heavy-duty machinery as direct-drive components of hydraulic systems. Due to their extremely high output torque and power density, the wet brake equipped with the hydraulic motors are necessary to achieve ultra-high braking torque in a compact space. However, due to a large number of internal friction pairs and small fit clearance between multiple friction pairs in wet brake, the rotation of the friction pairs in non-braking state will cause large friction torque loss and obvious temperature rise, thereby leading to the thermal failure of wet brake. How to optimize the structure of friction pairs to reduce the temperature rise of wet brake in non-braking state is a persistent challenge. Existing structure optimization design approaches of friction pairs in brakes mainly focus on the structure of each friction pair, which ignore the effect of fit clearance between the friction pairs on the temperature rise of brakes. Nevertheless, the fit clearance between friction pairs is an important factor that affect the temperature rise. For that, this study proposes a two-step structure optimization design approach of friction pairs for low-temperature rise wet brake in hydraculic motor, which simultaneously considers the fit clearance between the friction pairs and the structure of each friction pair. In this approach, the design process could be divided into two steps: firstly, the influence of fit clearance between multiple friction pairs on the temperature rise of wet brake in non-braking state is analyzed and optimized by the temperature rise theoretical model; secondly, in order to further reduce the temperature rise of wet brake, the oil groove structure of each friction plate are introduced and optimized by fluid-solid-thermal coupling simulation method. By this approach, the low-temperature rise structure of friction pairs with the optimized fit clearance between multiple friction pairs and oil grooves of each friction plate. Finally, a series of experiments are conducted to verify the effectiveness of the design approach. The result show that the temperature rise of wet brake could be effectively reduced 12 % by optimizing the structure of wet brake, demonstrating that the structure optimization design approach could provide a theoretical guidance to design low-temperature rise wet brake for large torque hydraulic motors.

BackgroundThis investigation seeks to ascertain the efficacy of various machine learning models in forecasting early neurological deterioration (END) following thrombolysis in patients with acute ischemic stroke (AIS).MethodsEmploying data from the Shenyang Stroke Emergency Map database, this multicenter study compiled information on 7,570 AIS patients from 29 comprehensive hospitals who received thrombolytic therapy between January 2019 and December 2021. An independent testing cohort was constituted from 2,046 patients at the First People’s Hospital of Shenyang. The dataset incorporated 15 pertinent clinical and therapeutic variables. The principal outcome assessed was the occurrence of END post-thrombolysis. Model development was executed using an 80/20 split for training and internal validation, employing classifiers like logistic regression with lasso regularization (lasso regression), support vector machine (SVM), random forest (RF), gradient-boosted decision tree (GBDT), and multi-layer perceptron (MLP). The model with the highest area under the curve (AUC) was utilized to delineate feature significance.ResultsBaseline characteristics showed variability in END incidence between the training (n = 7,570; END incidence 22%) and external validation cohorts (n = 2,046; END incidence 10%; p

Crop residue burning (CRB) is a major contributor to air pollution in China. Current fire detection methods, however, are limited by either temporal resolution or accuracy, hindering the analysis of CRB's diurnal characteristics. Here we explore the diurnal spatiotemporal patterns and environmental impacts of CRB in China from 2019 to 2021 using the recently released NSMC-Himawari-8 hourly fire product. Our analysis identifies a decreasing directionality in CRB distribution in the Northeast and a notable southward shift of the CRB center, especially in winter, averaging an annual southward movement of 7.5°. Additionally, we observe a pronounced skewed distribution in daily CRB, predominantly between 17:00 and 20:00. Notably, nighttime CRB in China for the years 2019, 2020, and 2021 accounted for 51.9%, 48.5%, and 38.0% respectively, underscoring its significant environmental impact. The study further quantifies the hourly emissions from CRB in China over this period, with total emissions of CO, PM10, and PM2.5 amounting to 12,236, 2,530, and 2,258 Gg, respectively. Our findings also reveal variable lag effects of CRB on regional air quality and pollutants across different seasons, with the strongest impacts in spring and more immediate effects in late autumn. This research provides valuable insights for the regulation and control of diurnal CRB before and after large-scale agricultural activities in China, as well as the associated haze and other pollution weather conditions it causes.

BackgroundWe aimed to use lactate dehydrogenase (LDH) as a marker of inflammation burden and quantify post-stroke inflammation’s direct and indirect effect on functional disability.MethodsWe analyzed 5,129 patients with acute ischemic stroke (AIS) admitted to Shenyang First People’s Hospital. Stroke recurrence and functional outcome measured by the modified Rankin Scale (mRS) were assessed at 90 days. Functional disability was defined as mRS score > 2. Receiver operating characteristic curve and restricted cubic spline (RCS) analysis were conducted to illustrate the associations between LDH levels and 90-day functional outcomes in patients with AIS. Mediation analyses were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between LDH and functional outcome. Positive correlation between LDH and hs-CRP was found and mediation effects of stroke recurrence in the association between LDH or hs-CRP and functional disability were both less than 20%. Sensitivity analyses in different subgroups showed comparable results.ResultsAmong 5,129 included AIS patients, the median (IQR) level of LDH was 186 (161–204.4) U/L. Functional disability was seen in 1200 (23.4%) patients and recurrence was observed in 371(7.2%) patients at 90-day follow-up. Each standard deviation increase in the concentration of LDH was linked to an increased risk of functional disability (adjusted odds ratio[aOR], 1.07; 95%CI,1.04–1.09) and stroke recurrence (aOR,1.02; 95%CI, 1.01–1.04) within 90 days. The highest quartile of LDH (>204.2 U/L) had an elevated risk of suffering functional disability (aOR, 1.21; 95%CI, 1.00–1.47) and recurrence (aOR, 1.21; 95%CI,1.00–1.47) compared with the lowest quartile of LDH (

Abstract Background To evaluate the effectiveness of instrument-assisted soft tissue mobilization (IASTM) on range of motion (ROM). Methods We performed a literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 23, 2023. Randomized controlled trials that compared treatment groups receiving IASTM to controls or IASTM plus another treatment(s) to other treatment(s) among healthy individuals with or without ROM deficits, or patients with musculoskeletal disorders were included. The Cochrane risk of bias tool was used to assess the risk of bias. Results Nine trials including 450 participants were included in the quantitative analysis. The IASTM was effective in improving ROM in degree in healthy individuals with ROM deficits and patients with musculoskeletal disorders (n=4) (MD = 4.94, 95% CI: 3.29 to 6.60), and in healthy individuals without ROM deficits (n=4) (MD = 2.32, 95% CI: 1.30 to 3.34), but failed to improve ROM in centimeter in healthy individuals with ROM deficits (n=1) (MD = 0.39, 95% CI: -1.34 to 2.11, p=0.66, I2 = 88%). Conclusions IASTM can improve ROM in degree in healthy individuals with or without ROM deficits, or in patients with musculoskeletal disorders (with very low to low certainty). Trial registration The PROSPERO registration ID is CRD42023425200.

Abstract Nighttime light remote sensing has been an increasingly important proxy for human activities. Despite an urgent need for long-term products and pilot explorations in synthesizing them, the publicly available long-term products are limited. A Night-Time Light convolutional LSTM network is proposed and applied the network to produce a 1-km annual Prolonged Artificial Nighttime-light DAtaset of China (PANDA-China) from 1984 to 2020. Assessments between modeled and original images show that on average the RMSE reaches 0.73, the coefficient of determination (R2) reaches 0.95, and the linear slope is 0.99 at the pixel level, indicating a high confidence in the quality of generated data products. Quantitative and visual comparisons witness PANDA-China’s superiority against other NTL datasets in its significantly longer NTL dynamics, higher temporal consistency, and better correlations with socioeconomics (built-up areas, gross domestic product, population) characterizing the most relevant indicator in different development phases. The PANDA-China product provides an unprecedented opportunity to trace nighttime light dynamics in the past four decades.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.

Abstract A significant portion of tight sandstone reservoirs commonly displays intricate fluvial channels or fault systems. Despite various attempts at analytical/semi-analytical modeling of multistage-fractured horizontal wells (MFHWs) in unconventional reservoirs, the majority of studies have focused on scenarios with homogeneous original physical properties, neglecting cases where MFHWs traverse multiple regions in channelized heterogeneous reservoirs. Comprehending the influence of heterogeneous and leaky faults on the performance of MFHWs is essential for efficient development. This study presents an innovative semi-analytical model to analyze the pressure transient behavior of MFHWs with secondary fractures as they traverse multiple regions in banded channel heterogeneous reservoirs, particularly considering the presence of partially-communicating faults. The approach combines the source method and Green’s function method to obtain solutions, introducing a novel technique for discretizing fractures without discretizing interfaces. The effects of the reservoir heterogeneity, partially-communicating faults and fractures system on pressure behavior are analyzed. The results indicate that the pressure behavior of MFHWs passing through regions with different physical properties exhibits distinctive characteristics, differing from both the homogeneous case and the heterogeneous cases where the well does not traverse distinct regions. Permeability heterogeneity influences the curves of all other flow regimes, except the early and late flow regimes. Faults affect transient pressure behavior only when not positioned in the middle of each two primary fractures. Region area heterogeneity primarily influences the medium flow regimes. This work provides valuable insights into the performance of MFHWs in channelized heterogeneous reservoirs, offering technical support for well testing in these reservoirs.

The corner element is the most basic constitutive element of multi-cellular thin-walled structures; however, scenarios for using relevant theories are limited. To improve this situation, this research investigated the effect of boundary conditions on the compression performance of corner elements with different angles. The deformation laws of corner elements were also explored. The approach was based on experiments and the finite element method. The result shows the outwardly extending plates on both sides yield first, the central twisted wire region then destabilizes and exits the working state, and the plate enters the post-buckling phase. A more relaxed boundary and larger angle can make it easier for the corner elements to trigger the symmetric deformation mode. Moreover, a mechanical model for simplified computation is proposed to predict the initial peak crushing force. The research can provide a reference for studying the compression performance of energy-absorbing elements in engineering.

Cadmium (Cd) is a highly hazardous toxic substance that can cause serious harm to animals. Previous studies have indicated that cadmium chloride (CdCl2) can damage organs, such as the liver, ovaries, and testicles. Naringenin (Nar) represents a flavonoid with various properties that promote the alleviation of Cd-induced damage. In this experiment, 60 chickens were divided into the control group, 150 mg/kg CdCl2 treatment group, 250 mg/kg Nar treatment group, and 150 mg/kg CdCl2 + 250 mg/kg Nar co-treatment group, which were treated for 8 weeks. Kidney tissues samples were collected to investigate kidney function, including oxidative stress (OS), endoplasmic reticulum (ER) stress, and autophagy activity. Experimental results showed the decreased weight of chickens and increased relative weight of their kidneys after CdCl2 treatment. The increase in NAG, BUN, Cr, and UA activities, as well as the increase in MDA and GSH contents, and the decrease activities of T-AOC, SOD, and CAT in the kidney, manifested renal injury by OS in the chickens. TUNEL staining revealed that CdCl2 induced apoptosis in renal cells. CdCl2 upregulates the mRNA and protein expression levels of GRP78, PERK, eIF2α, ATF4, ATF6, CHOP, and LC3, and inhibited the mRNA and protein expression levels of P62 proteins, which leads to ER stress and autophagy. The CdCl2 + Nar co-treatment group exhibited alleviated CdCl2-induced kidney injury, OS, ER stress, and autophagy. Research has demonstrated that Nar reduces CdCl2-induced kidney injury through alleviation of OS, ER stress, and autophagy.

BackgroundSarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients.MethodsPatients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA).ResultsA total of 480 patients with RA were included in the study (90% female, with the largest number in the 45–59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795–0.9498) and 0.907 (95% CI: 0.8552–0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility.ConclusionThis study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.

ABSTRACT: Lipopolysaccharide (LPS) from Gram-negative bacteria initially induces liver inflammation with proinflammatory cytokines expressions. However, the underlying hepatoprotective mechanism of quercetin on LPS-induced hepatic inflammation remains unclear. Specific pathogen-free chicken embryos (n = 120) were allocated control vehicle, PBS with or without ethanol vehicle, LPS (125 ng/egg) with or without quercetin treatment (10, 20, or 40 nmol/egg, respectively), quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated abovementioned solutions via the allantoic cavity. At embryonic d 19, the livers of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, and immunohistochemistry investigation. We found that the liver presented inflammatory response (heterophils infiltration) after LPS induction. The LPS-induced mRNA expressions of inflammation-related factors (TLR4, TNFα, IL-1β, IL-10, IL-6, MYD88, NF-κB1, p38, and MMP3) were upregulated after LPS induction when compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. Quercetin significantly decreased the immunopositivity to TLR4 and MMP3 in the treatment group when compared with the LPS group. Quercetin could significantly downregulate the mRNA expressions of autophagy-related genes (ATG5, ATG7, Beclin-1, LC3A, and LC3B) and necroptosis-related genes (Fas, Bcl-2, Drp1, and RIPK1) after LPS induction. Quercetin significantly decreased the immunopositivity to LC3 in the treatment group when compared with the LPS group; meanwhile, quercetin significantly decreased the protein expressions of LC3-I, LC3-II, and the rate of LC3-II/LC3-I. In conclusions, quercetin can alleviate hepatic inflammation induced by LPS through modulating autophagy and necroptosis.

Background Chronic sympathetic stimulation drives desensitization and downregulation of β1 adrenergic receptor (β1AR) in heart failure. We aim to explore the differential downregulation subcellular pools of β1AR signaling in the heart. Methods and Results We applied chronic infusion of isoproterenol to induced cardiomyopathy in male C57BL/6J mice. We applied confocal and proximity ligation assay to examine β1AR association with L‐type calcium channel, ryanodine receptor 2, and SERCA2a ((Sarco)endoplasmic reticulum calcium ATPase 2a) and Förster resonance energy transfer‐based biosensors to probe subcellular β1AR‐PKA (protein kinase A) signaling in ventricular myocytes. Chronic infusion of isoproterenol led to reduced β1AR protein levels, receptor association with L‐type calcium channel and ryanodine receptor 2 measured by proximity ligation (puncta/cell, 29.65 saline versus 14.17 isoproterenol, P