A domain-swapped CaMKII conformation facilitates linker-mediated allosteric regulation.

Ca2+ signaling plays a key role in physiological processes such as memory formation and cardiac function. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is the primary kinase that responds to Ca2+ inputs in these cells. There are four CaMKII paralogs in mammals which are alternatively spliced in the variable linker region to create upwards of 70 different variants. In this study, we systematically studied different linker regions and determined that the position of charged residues within the linker region modulates the Ca2+/CaM sensitivity of the holoenzyme. We present an X-ray crystal structure of full-length CaMKIIδ that shows a domain-swapped conformation of the subunits within the dodecameric holoenzyme. In this structure, the kinase domain of one subunit is docked onto the hub domain of a different subunit, providing an additional interface within the holoenzyme. Mutations at the equatorial and lateral interfaces revealed that the kinase-hub interaction dissociates as the hub-hub interfaces are disturbed, which led alterations in the stoichiometry of CaMKII holoenzyme and Ca2+/CaM sensitivity. Molecular dynamics simulations of linker-containing domain-swapped and non-domain-swapped CaMKIIs reveal that the domain-swapped configuration facilitates an interaction between the calmodulin binding domain and the variable linker region, such that dynamic electrostatic forces between charges on these segments can modulate the equilibrium between the compact and extended conformational states of the holoenzyme. Small angle X-ray scattering data confirms that a negatively charged linker CaMKII holoenzyme adopts a more compact conformation compared to a positively charged linker. These data support a model where patches of charged linker residues interact with the calmodulin binding domain to allosterically regulate sensitivity to Ca2+/CaM. Our findings provide a new framework for understanding CaMKII structure and allosteric regulation by the variable linker region in Ca2+-sensitive cells.

Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints.

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

Chitinase 3-like 1 expression associated with lymphatic metastasis and prognosis in urothelial carcinoma of the bladder.

Objectives: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods: We employed an RNA-sequencing cohort (n = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA-BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results: In our study, chitinase 3-like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P < 0.001). Within UCB tissues, CHI3L1 was expressed in both stromal cells (52.8%) and tumor cells (7.3%). Moreover, CHI3L1+ stromal cells, but not tumor cells, exhibited independent prognostic significance for both overall survival (P < 0.001) and recurrence-free survival (P = 0.006). CHI3L1+ stromal cells were positively associated with D2-40+ lymphatic vessel density (P < 0.001) and the immunosuppressive PD-L1/PD-1/CD8 axis in UCB tissues (all P < 0.05). A bioinformatics analysis also identified a positive association between CHI3L1 expression and lymphangiogenesis or immunosuppression pathways. Conclusion: Our study established a clear association between stromal CHI3L1 expression and lymphatic metastasis, suggesting that stromal CHI3L1 expression is a potential prognostic marker for bladder cancer patients.

Mechanically Enhanced Detoxification of Chemical Warfare Agent Simulants by a Two-Dimensional Piezoresponsive Metal-Organic Framework.

Chemical warfare agents (CWAs) refer to toxic chemical substances used in warfare. Recently, CWAs have been a critical threat for public safety due to their high toxicity. Metal-organic frameworks have exhibited great potential in protecting against CWAs due to their high crystallinity, stable structure, large specific surface area, high porosity, and adjustable structure. However, the metal clusters of most reported MOFs might be highly consumed when applied in CWA hydrolysis. Herein, we fabricated a two-dimensional piezoresponsive UiO-66-F4 and subjected it to CWA simulant dimethyl-4-nitrophenyl phosphate (DMNP) detoxification under sonic conditions. The results show that sonication can effectively enhance the removal performance under optimal conditions; the reaction rate constant k was upgraded 45% by sonication. Moreover, the first-principle calculation revealed that the band gap could be further widened with the application of mechanical stress, which was beneficial for the generation of 1O2, thus further upgrading the detoxification performance toward DMNP. This work demonstrated that mechanical vibration could be introduced to CWA protection, but promising applications are rarely reported.

Engineering of Cerium Modified TiNb2O7 Nanoparticles For Low-Temperature Lithium-Ion Battery.

Although TiNb2O7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li4Ti5O12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li+ and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g-1 at 100 mA g-1 after 100 cycles, and 183.0 mA h g-1 even under 3200 mA g-1. In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g-1 can still reach 89.7 mA h g-1, corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature.

[Hydrochemical Characteristics, Controlling Factors and Water Quality Evaluation of Shallow Groundwater in Tan-Lu Fault Zone （Anhui Section）].

To study the hydrochemical characteristics, controlling factors, and groundwater quality of the Tan-Lu fault zone (Anhui section), 86 groundwater samples were taken from the areas surrounding the Tan-Lu fault zone (Anhui section), which included the Jianghuai Wavy Plain, the Yanjiang Hill Plain, and the Dabie Mountains in western Anhui. Descriptive statistics, Piper diagram, Gibbs diagram, ion ratio analysis, saturation index, chloride-alkalinity index, and entropy weight water quality index (EWQI) were used to comprehensively study the hydrochemical characteristics and controlling factors of groundwater and to evaluate its quality. The results showed that the shallow groundwater in the Tan-Lu fault zone (Anhui section) was weakly alkaline, with dominant anions and cations of HCO3-, Ca2+ and Na+, respectively, and the hydrochemical types were mainly HCO3-Ca·Mg and HCO3-Na·Ca. The solute source of groundwater was mainly controlled by water-rock interactions, and the weathering of silicate and carbonate rocks jointly contributed to the formation of the chemical components of groundwater. Strong cation exchange adsorption was an important factor causing Na+ enrichment. The overall quality of groundwater in the study area was good but was polluted to a certain extent by human activities. Most of the groundwater in the Jianghuai Wavy Plain and Yanjiang Hill Plain was not suitable for direct drinking. The results of this research have important implications for the sustainable development and utilization of shallow groundwater resources and environmental protection in the Tan-Lu fault zone (Anhui section).

SASAN: Spectrum-Axial Spatial Approach Networks for Medical Image Segmentation.

Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss (LSM), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.

Development of a novel humanized anti-TSLP monoclonal antibody HZ-1127 with anti-allergic diseases and cancer potential.

Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family and has been widely recognized as a master regulator of type 2 inflammatory responses at barrier surfaces. Recent studies found dysregulation of the TSLP-TSLP receptor (TSLPR) pathway is associated with the pathogenesis of not only allergic diseases but also a wide variety of cancers including both solid tumors and hematological tumors. Thus, the blockade of TSLP represents an attractive therapeutic strategy for allergic diseases and cancer. In this study, we report the development of a novel humanized anti-TSLP monoclonal antibody (mAb) HZ-1127. Binding affinity, specificity, and ability of HZ-1127 in inhibiting TSLP were tested. HZ-1127 selectively binds to the TSLP cytokine with high affinity and specificity. Furthermore, HZ-1127 dramatically inhibits TSLP-dependent STAT5 activation and is more potent than Tezepelumab, which is an FDA-approved humanized mAb against TSLP for severe asthma treatment in inhibiting TSLP-induced CCL17 and CCL22 chemokines secretion in human peripheral blood mononuclear cells. Our pre-clinical study demonstrates that HZ-1127 may serve as a potential therapeutic agent for allergic diseases and cancer.

Chip-level mass detection for micro-LED displays based on regression analysis and deep learning.

Though micro-light-emitting diode (micro-LED) displays are regarded as the next-generation emerging display technology, challenges such as defects in LED's light output power and radiation patterns are critical to the commercialization success. Here we propose an electroluminescence mass detection method to examine the light output quality from the on-wafer LED arrays before they are transferred to the display substrate. The mass detection method consists of two stages. In the first stage, the luminescent image is captured by a camera by mounting an ITO (indium-tin oxide) transparent conducting glass on the LED wafer. Due to the resistance of the ITO contact pads and on-wafer n-type electrodes, we develop a calibration method based on the circuit model to predict the current flow on each LED. The light output power of each device is thus calibrated back by multi-variable regression analysis. The analysis results in an average variation as low as 6.89% for devices predicted from luminescent image capturing and actual optical power measurement. We also examine the defective or non-uniform micro-LED radiation profiles by constructing a 2-D convolutional neural network (CNN) model. The optimized model is determined among three different approaches. The CNN model can recognize 99.45% functioning LEDs, and show a precision of 96.29% for correctly predicting good devices.

Structural basis for human Cav3.2 inhibition by selective antagonists.

The Cav3.2 subtype of T-type calcium channels has been targeted for developing analgesics and anti-epileptics for its role in pain and epilepsy. Here we present the cryo-EM structures of Cav3.2 alone and in complex with four T-type calcium channel selective antagonists with overall resolutions ranging from 2.8 Å to 3.2 Å. The four compounds display two binding poses. ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration. TTA-P2 and ML218 project their 3,5-dichlorobenzamide groups into the II-III fenestration and place their hydrophobic tails in the cavity to impede ion permeation. The fenestration-penetrating mode immediately affords an explanation for the state-dependent activities of these antagonists. Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity.

Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Transcatheter or Surgical Aortic Valve Replacement in Women with Small Annuli at Low or Intermediate Surgical Risk.

There are limited data from randomized controlled trials assessing the impact of transcatheter aortic valve replacement (TAVR) or surgery in women with aortic stenosis and small aortic annuli. We evaluated 2-year clinical and hemodynamic outcomes following AVR to understand acute valve performance and early and mid-term clinical outcomes. This post hoc analysis pooled women enrolled in the randomized, prospective, multicenter Evolut Low Risk and SURTAVI intermediate risk trials. Women with severe aortic stenosis at low or intermediate surgical risk who had a computed-tomography-measured annular perimeter of ≤ 72.3 mm were included and underwent self-expanding, supra-annular TAVR or surgery. The primary endpoint was 2-year all-cause mortality or disabling stroke rate. The study included 620 women (323 TAVR, 297 surgery) with a mean age of 78 years. At 2 years, all-cause mortality or disabling stroke was 6.5% for TAVR and 8.0% for surgery, p = 0.47. Pacemaker rates were 20.0% for TAVR and 8.3% for surgery, p <0.001. The mean effective orifice area at 2 years was 1.9 ± 0.5 cm2 for TAVR and 1.6 ± 0.5 cm2 for surgery, and the mean gradient was 8.0 ± 4.1 mmHg vs 12.7 ± 6.0 mmHg, respectively (both p <0.001). Moderate or severe patient-prothesis mismatch at discharge occurred in 10.9% of TAVR and 33.2% of surgery patients, p < 0.001. In conclusion, in women with small annuli, clinical outcomes to 2 years were similar between self-expanding, supra-annular TAVR and surgery, with better hemodynamics in the TAVR group, and fewer pacemakers in the surgical group.

Relationship between Pain and Dementia: The Mediating Effect of Depression among Chinese Elderly.

BACKGROUND: Chronic pain poses a significant problem for older adults and may potentially impact cognitive function. This study aimed to examine the cross-sectional relationship between pain severity and cognitive function in elderly individuals residing in the community. Additionally, this study sought to examine the mediating effect of depression on the relationship between pain and dementia. METHODS: The study sample was derived from the 2018 China Health and Aging Longitudinal Study (CHARLS), comprising cross-sectional data from 4559 community residents aged 65 years or older. The primary outcome assessed was the occurrence of dementia, while the main independent variable was pain severity (none, little, somewhat, quite a bit, very). Depression score served as the mediating factor. Chi-square and binary logistic regression analyses were performed to examine the relationship between depression and the occurrence of pain and dementia. An intermediate model was constructed by stepwise regression. RESULTS: The study indicates a significant association between cognitive impairment and both chronic pain and depressive symptoms in older adults living in China. Individuals who frequently report experiencing pain exhibit a higher likelihood of developing dementia when compared to those who do not report any pain (odds ratio (OR) = 1.72, p < 0.001). Moreover, depressive symptoms significantly mediate the relationship between pain and dementia, with the mediating effect accounting for 65.25%. CONCLUSIONS: Chronic pain not only directly impacts patients' cognitive function but also indirectly exacerbates cognitive impairment through depressive symptoms as a mediating variable. For elderly individuals experiencing depressive symptoms, it is important to provide appropriate psychological treatment in conjunction with pain management strategies.

Construction of A Smart Hospital Innovation Platform Using the Internet + Technology.

Objective: This study aims to investigate the practical application of "Internet + technology" leveraging medical big data to enhance the development of a smart hospital platform. Specifically, the focus is on optimizing patient care processes, refining medical data management systems, and enhancing operational efficiency within the hospital setting. Methods: With the help of traditional Internet and mobile Internet technology, we analyzed the patient behavior big data accumulated in our hospital for many years, simplified the diagnosis and treatment links, refined the service connotation, and improved patient satisfaction before, during and after diagnosis; With the help of barcode, RFID and 5G networks, the links that are easy to produce medical security incidents can be monitored to improve medical quality, such as digital operating room system, establishment of multidisciplinary consultation center (MDT), electronic medical record system based on digital signature, etc.; Integrate the existing data of human resources, equipment and consumables, drugs, general supplies and finance, establish the hospital ERP system, introduce BI, and realize the dynamic monitoring of revenue and cost; Artificial intelligence technologies such as natural language processing (NLP) and machine learning are used to extract, clean, transform and analyze a large number of hospital medical information data to form a medical data platform, which can assist the hospital knowledge base to be applied in diagnosis and treatment, clinical research, clinical medicine, clinical medicine and other fields. The effectiveness of these technologies was assessed through a comprehensive analysis of their impact on patient care processes, medical data management, and overall operational efficiency within the hospital setting. Results: The study yielded significant outcomes across three critical domains. Firstly, in patient care, the implementation of expanded mobile medical services, mobile applications for records and rounds, and the establishment of digital signature-based records and intelligent surgical assistance enhanced accessibility and quality of care. Secondly, operational efficiency was notably improved through the integration of ERP and BI systems, streamlining resource management and surgical procedures. Lastly, advancements in data management, including the development of a medical data platform and the deployment of AI technologies, facilitated efficient analysis and utilization of clinical data. Quantitatively, reductions in patient visit time and medical costs were observed, alongside improved diagnostic accuracy facilitated by comprehensive records. These findings collectively underscore the transformative impact of "Internet + technology" integration on hospital operations and patient outcomes. Conclusion: The integration of "Internet + technology" in a smart hospital setting has demonstrated numerous benefits. This study has revealed novel findings regarding the tangible improvements in patient outcomes and hospital efficiency resulting from technology integration. Specifically, the implementation of mobile medical services, digital records, and AI-driven systems has led to significant reductions in patient visit times and medical costs. Moreover, the streamlining of operational processes through ERP and BI systems has enhanced resource management and surgical procedures. These findings underscore the transformative potential of technology in revolutionizing healthcare delivery, ultimately leading to better patient care and operational effectiveness in smart hospital environments.

Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.