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Abstract This study aimed to investigate whether lymphocyte-C-reactive protein ratio (LCR) upon admission can predict disease progression and intensive care unit (ICU) admission in adult patients with diabetic ketoacidosis (DKA). A single-center retrospective study was conducted, including adult DKA patients admitted to the First Affiliated Hospital of Harbin Medical University between March 2018 and March 2023. Multiple demographic and clinical data were collected from the medical records upon admission and during hospitalization. Subsequently, sequential organ failure assessment (SOFA) score and LCR were calculated based on relevant clinical parameters within 24 h of admission. These indicators were compared among different disease severity groups, and factors related to severe DKA, concurrent acute kidney injury (AKI), and ICU admission were further analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity, specificity, area under the ROC curve (AUC), and cut-off value of LCR. A total of 271 adult DKA patients were enrolled and categorized into three groups: mild group (n = 42), moderate group (n = 64), and severe group (n = 165). Significant differences in demographic and clinical data were observed among these groups. Glasgow coma scale (GCS) score, LCR, pH, and bicarbonate (HCO3 -) were identified as protective factors for severe DKA. Conversely, SOFA score, neutrophil count (NEUT), serum creatinine (SCr), and glucose (GLU) were risk factors for concurrent AKI. Concurrent AKI and SOFA score were risk factors for ICU admission, while pH was a protective factor. The areas under the ROC curve (AUC) of LCR to classify adult DKA patients into mild group, severe group, and ICU admission were 0.679, 0.718, and 0.621, respectively, with cut-off value of 212.80, 96.16, and 63.35, sensitivity of 54.8%, 76.4%, and 78.9%, and specificity of 76.0%, 62.4%, and 46.3%. LCR upon admission provides great potential to predict disease progression and ICU admission in adult patients with DKA.

Highlights 1. Microscopic flow models are established considering the mechanical response in massive flooding and massive soaking. 2. The influence characteristics of the factors affecting massive energy replenishment are quantitatively revealed. 3. The differences of microscopic flow mechanism are compared in conventional and massive energy replenishment.

Abstract Objectives To differentiate novel coronavirus pneumonia (NCP) with influenza A virus (IAV) pulmonary infection based on computed tomography (CT) radiomics features combined with clinical feature. Methods A total of 292 patients were enrolled, as NCP determined with reverse-transcription polymerase chain reaction (RT-PCR) and abnormal chest CT findings and IAV pulmonary infection confirmed by nucleic acid test with pneumonia lesion in the chest CT, retrospectively. The dataset was randomly divided into 233 cases in the training set and 59 cases in the validation set according to the ratio of 8:2, and there were 107 cases collected for verification as external test set. Firstly, voxel-based gray-level discretization (binWidth = 25) and Z-Score normalization were applied to preprocess the patient's ROI and normalize the extracted features. Then, the most predictive radiomic features were selected and their corresponding coefficients were evaluated using the correlation coefficient algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Subsequently, univariate logistic regression was employed to screen for clinically discriminative features from the patient's clinical characteristics. Finally, constructing the radiomics model and clinical model using support vector machines and logistic regression methods, respectively. And then combining these features of the two to construct a combined model. Receiver operating characteristic curve (ROC), calibration curve, and decision curve were performed to evaluate the classification of the radiomics model, clinical model and combined model. Area under ROC curve (AUC) were calculated to evaluate the diagnostic efficiency, and Delong’s test was used to compare the AUC between different models. Results Age, white blood cells, neutrophils, lymphocytes, and basic diseases reached statistical significance in the training set. After LASSO, 16 optimal radiomics features were retained. In the validation set and external test set, the SVM radiomics model achieved AUCs of 0.818 and 0.808 for automatic classification of NCP and IAV pulmonary infection,; and the clinical classification model shad AUCs were 0.676 and 0.669; finally, the 5 clinical features and the 16 selected radiomics features were used to construct the combined model with the AUCs of 0.821 and 0.820. After incorporating clinical features, the clinical model’s discriminatory and predictive efficacy further improved in testing sets (AUC, 0.669 vs. 0.820, P = 0.002). The combined model performed well for differentiating the NCP and IAV pulmonary infection, and the calibration curves showed good agreement and decision curves indicated relatively satisfactory clinical benefits. Conclusion The proposed combined model is feasible and effective in differentiating the NCP and IAV pulmonary infection, which may be used as a convenient and efficient auxiliary tool for radiologists to diagnose noninvasively based on the imaging structure of CT.

Abstract The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman’s correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

Abstract Huff‐n‐puff (HnF) is a crucial technology for effectively enhancing the oil recovery (EOR) of tight oil reservoirs. Soaking period is the primary platform for injection medium interacting with formation fluid and reservoir rock in HnF. Elucidating the micro‐percolation mechanism of the soaking period is immensely significant for guiding oilfield production practices. The present study established a physical simulation method combining HnF experiments with nuclear magnetic resonance to reveal the microscopic percolation mechanisms, including water, fracturing fluid, and surfactant. Furthermore, the impacts of soaking time, HnF cycles, wettability, and pore structure on oil recovery degree were quantified. The results demonstrate the crucial significance of wettability and pore structure in the soaking period. The dominant mechanism during water HnF in reservoirs characterized by well‐connected pore networks and minimal clay pores is micropore imbibition, while conversely, macropore displacement plays a predominant role. The oil recovery degree of fracturing fluid HnF primarily relies on mitigating solid‐fluid forces within macropores. The surfactant HnF in preferential water‐ and oil‐wet reservoirs is primarily governed by oil films stripped from macropore walls and micropore imbibition, respectively. Specifically, water and fracturing fluid HnF are suitable for shorter soaking time and fewer HnF cycles, whereas the surfactant HnF exhibits an inverse relationship.

Abstract Satellite-based Quantitative Precipitation Estimates (QPE) are indirect estimates of precipitation rates and as such are often prone to errors, warranting a need for characterizing the associated uncertainties before being used in application-specific studies. Moreover, multiple satellite-based QPE products are offered through different agencies, each with their own specifications, formats and requirements, posing a challenge to understanding the products uncertainties. This manuscript presents a standardized validation system named NPreciSe – NOAA Satellite-based Precipitation Validation System, which assesses the performance of satellite-based precipitation products in near real-time over the continental United States. NPreciSe is coupled with a user-interactive web platform and built using an open-source software, Python. It is structured to help (1) the end-users determine the best satellite QPE for their specific application, and (2) the algorithm developers identify systematic biases in QPE retrievals. This manuscript presents the capabilities of the NPreciSe, discusses the methodology adopted in developing the standardized validation system, and introduces the web portal.

Abstract Background Kidney Renal Clear Cell Carcinoma (KIRC) is a common malignant tumor of the urinary system, and its incidence is increasing. ERBB3 binding protein (EBP1) is upregulated in various cancers. However, the connection between EBP1 and KIRC has not been reported. Methods The expression of EBP1 in normal kidney tissue and KIRC tissue was analyzed through database and tissue microarray. EBP1 was knocked down in KIRC cell lines, and its impact on KIRC proliferation was assessed through CCK-8, soft agar assay, and flow cytometry. Scratch and transwell assays were used to evaluate the influence of EBP1 on KIRC invasion and migration. Nude mice tumor experiment were conducted to examine the effect of EBP1 on tumor tissue. Database analysis explored potential pathways involving EBP1, and validation was performed through Western blot experiments and p38 inhibitor. Results EBP1 is upregulated in KIRC and significantly correlates with clinical staging, pathological grading, and lymph node metastasis in patients. The mechanism research showed that knocking down EBP1 inhibited KIRC proliferation, invasion, and migration and inhibited p38 phosphorylation and the expression of hypoxia-inducible factor-1α (HIF-1α) in KIRC. p-38 inhibitor (SB203580) inhibits p38 phosphorylation and HIF-1α expression and suppresses cell viability in a concentration-dependent manner, but has no effect on EBP1 expression. HEK 293T cells overexpressing EBP1 showed increased expression of phosphorylated p38 and HIF-1α and enhanced cell viability, however, SB203580 inhibited this effect of EBP1. Conclusion EBP1 may promote the occurrence and development of KIRC by regulating the expression of p38/HIF-1α signaling pathway. Graphical Abstract

Abstract From degeneration causing intervertebral disc issues to trauma‐induced meniscus tears, diverse factors can injure the different types of cartilage. This review highlights adhesives as a promising and rapidly implemented repair strategy. Compared to traditional techniques such as sutures and wires, adhesives offer several advantages. Importantly, they seamlessly connect with the injured tissue, deliver bioactive substances directly to the repair site, and potentially alleviate secondary problems like inflammation or degeneration. This review delves into the cutting‐edge advancements in adhesive technology, specifically focusing on their effectiveness in cartilage injury treatment and their underlying mechanisms. We begin by exploring the material characteristics of adhesives used in cartilage tissue, focusing on essential aspects like adhesion, biocompatibility, and degradability. Subsequently, we investigate the various types of adhesives currently employed in this context. Our discussion then moves to the unique role adhesives play in addressing different cartilage injuries. Finally, we acknowledge the challenges currently faced by this promising technology.

Abstract Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of C sp2 -H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.

Abstract To validate a radiomics model based on multi-sequence magnetic resonance imaging (MRI) in predicting the ki-67 expression levels in early-stage endometrial cancer, 131 patients with early endometrial cancer who had undergone pathological examination and preoperative MRI scan were retrospectively enrolled and divided into two groups based on the ki-67 expression levels. The radiomics features were extracted from the T2 weighted imaging (T2WI), dynamic contrast enhanced T1 weighted imaging (DCE-T1WI), and apparent diffusion coefficient (ADC) map and screened using the Pearson correlation coefficients (PCC). A multi-layer perceptual machine and fivefold cross-validation were used to construct the radiomics model. The receiver operating characteristic (ROC) curves analysis, calibration curves, and decision curve analysis (DCA) were used to assess the models. The combined multi-sequence radiomics model of T2WI, DCE-T1WI, and ADC map showed better discriminatory powers than those using only one sequence. The combined radiomics models with multi-sequence fusions achieved the highest area under the ROC curve (AUC). The AUC value of the validation set was 0.852, with an accuracy of 0.827, sensitivity of 0.844, specificity of 0.773, and precision of 0.799. In conclusion, the combined multi-sequence MRI based radiomics model enables preoperative noninvasive prediction of the ki-67 expression levels in early endometrial cancer. This provides an objective imaging basis for clinical diagnosis and treatment.

Abstract In order to address the shortcomings of traditional anonymity network anonymity evaluation methods, which only analyze from the perspective of the overall network and ignore the attributes of individual nodes, we proposes a dynamic anonymity model based on a self-built anonymous system that combines node attributes, network behavior, and program security monitoring. The anonymity of evaluation nodes is assessed based on stable intervals and behavior baselines defined according to their normal operating status. The anonymity of the network is evaluated using an improved normalized information entropy method that refines anonymity evaluation to the anonymity of each node and expands the dimensionality of evaluation features. This paper compares the effectiveness of our proposed method with static framework information entropy and single indicator methods by evaluating the degree of anonymity provided by a self-built Tor anonymous network under multiple operating scenarios including normal and under attack. Our approach utilizes dynamically changing network anonymity based on multiple anonymous attributes and better reflects the degree of anonymity in anonymous systems.

PurposeThis study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs.Materials and methodsIn a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p

Abstract RNA interference (RNAi) is a powerful tool for understanding and manipulating signaling pathways in plant science, potentially facilitating the accelerated development of novel plant traits and crop yield improvement. The common strategy for delivering siRNA into intact plants using agrobacterium or viruses is complicated and time‐consuming, limiting the application of RNAi in plant research. Here, a novel delivery method based on mesoporous silica nanoparticles (MSNs) is reported, which allows for the efficient delivery of siRNA into mature plant leaves via topical application without the aid of mechanical forces, achieving transient gene knockdown with up to 98% silencing efficiency at the molecular level. In addition, this method is nontoxic to plant leaves, enabling the repeated delivery of siRNA for long‐term silencing. White spots and yellowing phenotypes are observed after spraying the MSN‐siRNA complex targeted at phytoene desaturase and magnesium chelatase genes. After high light treatment, photobleaching phenotypes are also observed by spraying MSNs‐siRNA targeted at genes into the Photosystem II repair cycle. Furthermore, the study demonstrated that MSNs can simultaneously silence multiple genes. The results suggest that MSN‐mediated siRNA delivery is an effective tool for long‐term multi‐gene silencing, with great potential for application in plant functional genomic analyses and crop improvement.

BackgroundHigh-quality in-forest landscapes are very important when landscape designers and foresters are planning and managing forest landscape resources. Understanding people’s visual behavior toward in-forest landscapes plays an important role in creating high-quality in-forest landscapes.MethodsPeople’s visual information about in-forest landscapes with different landscape uniformity (IFLDLU) was visualized and digitized by eye-tracking technology and virtual reality method of picture, and the data were statistically analyzed by MANOVA, one-way ANOVA, Spearman’s rho correlation analysis, and linear regression in SPSS.PurposeThis study aimed to discuss the influence of landscape uniformity on people’s visual behavior, satisfaction preference, and re-viewing intention, and to reveal the main reasons for the spatial cognitive characteristics of in-forest scenes that arouse their visual attention and re-viewing intention.Main results(1) The landscape uniformity of the in-forest landscape (IFL) affects people’s observation mode; (2) People’s visual attention differs across in-forest landscape uniformity, as mainly reflected in visual span and pupil diameter; (3) Overall, people prefer a cluster distribution of in-forest landscapes, for which they have higher re-viewing intentions; (4) Spatial cognitive characteristics that arouse participants’ visual behavior, satisfaction preference, and re-viewing intention vary with the landscape uniformity of in-forest landscapes. Among them, many spatial cognitive characteristics should be optimized in random distribution for IFL, arousing higher satisfaction preference and re-viewing intention. Therefore, when planning, designing, and managing in-forest landscapes, we suggest that spatial cognitive characteristics should be improved and optimized based on the landscape uniformity of the IFL to arouse participants’ positive visual attention, enhance their place identity, make them “reluctant to bid farewell,” and further arouse their place attachment.

Objective To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). Methods This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. Results This study included 145 patients assigned to moderate ( n = 105), severe ( n = 33) and critical groups ( n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of −0.564, −0.548, −0.550 and −0.429 at four different times. Conclusion Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

Abstract Skeletal muscle disease severity can often progress asymmetrically across muscle groups and heterogeneously within tissues. An example is Duchenne Muscular Dystrophy (DMD) in which lack of dystrophin results in devastating skeletal muscle wasting in some muscles whereas others are spared or undergo hypertrophy. An efficient, non-invasive approach to identify sites of asymmetry and degenerative lesions could enable better patient monitoring and therapeutic targeting of disease. In this study, we utilized a versatile intravenously injectable mesoporous silica nanoparticle (MSNP) based nanocarrier system to explore mechanisms of biodistribution in skeletal muscle of mdx mouse models of DMD including wildtype, dystrophic, and severely dystrophic mice. Moreover, MSNPs could be imaged in live mice and whole muscle tissues enabling investigation of how biodistribution is altered by different types of muscle pathology such as inflammation or fibrosis. We found MSNPs were tenfold more likely to aggregate within select mdx muscles relative to wild type, such as gastrocnemius and quadriceps. This was accompanied by decreased biodistribution in off-target organs. We found the greatest factor affecting preferential delivery was the regenerative state of the dystrophic skeletal muscle with the highest MSNP abundance coinciding with the regions showing the highest level of embryonic myosin staining and intramuscular macrophage uptake. To demonstrate, muscle regeneration regulated MSNP distribution, we experimentally induced regeneration using barium chloride which resulted in a threefold increase of intravenously injected MSNPs to sites of regeneration 7 days after injury. These discoveries provide the first evidence that nanoparticles have selective biodistribution to skeletal muscle in DMD to areas of active regeneration and that nanoparticles could enable diagnostic and selective drug delivery in DMD skeletal muscle.

BackgroundInitial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections.Case summaryIn this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid.ConclusionAlthough contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.

In order to identify and evaluate reservoir wettability, so as to select suitable mining methods to improve oil recovery, wettability evaluation through one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) technology combined with physical simulation experiments was carried out in this study, and the feasibility of the experimental method was verified by contact Angle method. According to the principle of hydrophilic inorganic content and hydrophobic organic content of shale, the wettability can be evaluated through vacuum self-imbibition oil and self-imbibition water physical simulation experiments combined with 1D NMR technology, that is, total water absorption can be considered as inorganic content, organic content can be obtained by subtracting total water absorption from total oil absorption, and adsorbed oil content can be obtained by subtracting pore volume from total oil absorption. In addition to the wettability measurement by contact Angle method to verify the experimental method, the occurrence ratio of adsorbed oil can also be verified twice by 2D NMR spectrum. The results show that the error between the proportion of adsorbed oil measured by 2D NMR spectrum and that measured by self-imbibition method is within 4%. In the saturated oil-bound water state, the bound water is within the relaxation interval of 110 ms and T2>10 ms. And the relaxation time of aqueous phase moved to the right compared with that in the saturated water state, the interaction force between water and the pore wall was weakened, showing the characteristics of free fluid, and the rock sample became oil-wet, which was consistent with the wettability results measured by contact Angle. Therefore, the wettability of rock samples can be evaluated by 1D NMR technique combined with vacuum imbibition method, or by analyzing the changes of NMR spectra of aqueous phase in completely saturated water and saturated oil-bound water.

Objectives To elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA).Methods This was a 5-year prospective study. Patients with consecutive ERA without overt cardiovascular disease (CVD) were recruited to receive 1 year of tight-control treatment followed by standard-of-care management. High-resolution carotid ultrasound was assessed at baseline and year 5. The primary outcome was subclinical atherosclerosis progression (AP+), defined as the occurrence of incident plaque, increased region harbouring plaques and/or maximum carotid intima-media thickness progression ≥0.9 mm at year 5. Inflammatory burden during the follow-up period was represented by the cumulative average Disease Activity Score 28-erythrocyte sedimentation rate (ca-DAS28-ESR). Persistent low disease activity (LDA) or remission state was defined as ca-DAS28-ESR≤3.2.Results One-hundred and four patients with ERA (age: 52±11 years, 81 (77.9%) female) were included in this analysis. Fifty-two (50%) patients achieved persistent LDA or remission and 42 patients (40.4%) had AP+. Patients in the AP+ group were older and had more traditional cardiovascular risk factors at baseline. Multivariate logistic regression analysis revealed that patients with persistent moderate or high disease activity (ca-DAS28-ESR>3.2) had a significantly increased risk of AP+ (OR 5.05, 95% CI 1.53, 16.64, p=0.008) compared with those who achieved persistent remission. The risk of AP+ was similar in patients who achieved persistent LDA and remission.Conclusions Achieving persistent LDA or remission may prevent progression of atherosclerosis in ERA. A treat-to-target approach aiming at sustained LDA or remission may reduce the risk of CVD by preventing AP+.

Abstract The Hammett equation is commonly used to theoretically depict the remote electronic effects of substituents on catalytic activities of metal nodes of metal-organic frameworks (MOFs). However, the application of the theory to MOF catalysts usually encounters problems because it relies heavily on empirical parameters with unknown transferability. To develop an alternative prediction theory, the linker orbital energy model has been proposed by density functional theory calculations. The model provides a simple method to approximately depict the remote electronic substituent effects on catalytic activities of metal nodes of MOFs, and its general applicability to MOFs is supported by extensively revisiting the structure-activity relationships reported in the literatures. The model can be used to design catalytic activity of metal nodes of MOFs by engineering the electronic properties of linkers and substituents.

Abstract The research presented in this paper introduces a novel environmental energy‐harvesting technology that harnesses electricity from the evaporation of water using porous structural materials. Specifically, a strategy employing paper‐based hydroelectric generators (p‐HEGs) is proposed to capture the energy produced during water evaporation and convert it into usable electricity. The p‐HEGs offer several advantages, including simplicity in fabrication, low cost, and reusability. To evaluate their effectiveness, the water evaporation‐induced electrical output performance of four different p‐HEGs are compared. Among the variants tested, the p‐HEG combining wood pulp and polyester fiber exhibits the best output performance. At room temperature, this particular p‐HEG generates a short‐circuit current and open‐circuit voltage of ≈0.4 µA and 0.3 V, respectively, thereby demonstrating excellent electrical stability. Furthermore, the electrical current and voltage generated by the p‐HEG through water evaporation are able to power an LED light, both individually and in series and parallel connections. This study delves into the potential of electricity harvesting from water evaporation and establishes it as a viable method for renewable energy applications.

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1β and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.

Abstract A nano‐enabled drug delivery acupuncture technology (nd‐Acu) is developed that is based on traditional acupuncture needles where the stainless‐steel surface is designed to deliver various payload molecules. To create the nd‐Acu platform, an electrochemistry procedure is used to attach methyl salicylate‐modified cyclodextrin in which the sugar rings allow the encapsulation of structurally defined single or multiple payload molecules via an inclusion complexation process. Drug loading and release profile are first studied using fluorescent dyes abiotically and at intact animal level. nd‐Acu allows more efficient dye loading and time‐dependent release compared to pristine needles without cyclodextrin modification. Subsequently, a proof‐of‐principle efficacy study is conducted using the platform to load a local anesthetic, lidocaine, for the treatment of knee osteoarthritis (KOA) in mice. It is demonstrated that lidocaine‐laden nd‐Acu can effectively alleviate pain, reduce inflammation, and slow down KOA development biochemically and histologically. Hypothesis‐driven and proteomic approaches are utilized to investigate the working mechanisms of lidocaine nd‐Acu, indicating that the therapeutic outcome is attributed to the in vivo modulation of the HMGB1/TLR4 signaling pathway. The study also obtained preliminary evidence suggesting the involvement of mitochondria as well as small GTPase such as cdc42 during the treatment by lidocaine nd‐Acu.

Children with developmental disabilities may develop emotional and behavioral problems that arise from difficulties in social interaction, and therefore, a process of providing and testing intervention activities for emotional and behavioral issues in the early stages of development is required. This study evaluated the effects of a 12-week service-learning exercise program on children with developmental disabilities, contrasting it with a control group not engaged in specific physical activities. The participants included 18 children with developmental disabilities who participated in the service-learning exercise program (SLG) and 18 children with developmental disabilities (Non-SLG) who did not participate. The Korean Behavior Assessment System for Children-2 was used to evaluate children’s emotional and behavioral problems. A two-way repeated-measures ANOVA was conducted to verify the interaction effect between the group and period according to program participation. The results showed the positive internalization of problem behaviors in the emotional domain (F = 4.291, p = 0.011), attention deficit/hyperactivity (F = 4.761, p = 0.012), and personal adjustment (F = 4.116, p = 0.023) in the SLG group. These results suggest that participation in a service-learning exercise program positively affected emotional and behavioral problems in children with developmental disabilities. This could provide a basis for future research on service-learning exercise programs for children with developmental disabilities.

Researchers often report higher metabolic syndrome (MetS) pr\4;evalence among cancer survivors than among non-cancer individuals. This study aims to explore the impact of cancer presence, activity type, and dietary lifestyle on MetS in males over 40 years of age. Participants (n = 9846; 618 cancer survivors, 9228 non-cancer) were selected by extracting data from a Korean government database spanning the years 2016 to 2021. Physical activity patterns, dietary habits, and MetS factors were measured, and a multiple logistic regression analysis was statistically processed for an odds ratio (OR). MetS was present in 32.8% of cancer survivors and 28.6% of non-cancer individuals. Gastric cancer survivors exhibited a 16% lower OR for MetS versus non-cancer participants. The ORs were higher by 1.60-, 1.45-, and 1.26-fold for colorectal, urinary, and other cancers, respectively. Cancer survivors with high calorie, carbohydrate, and fat intakes exhibited ORs of 2.01 (95% CI 1.28−4.04), 2.33 (95% CI 1.28−4.54), and 1.39 (95% CI 1.05−2.37) compared to the recommended level. The high fiber-intake group reduced the MetS OR by 20%. In conclusion, The MetS prevalence was higher in survivors with colorectal cancer, urinary cancer, and other cancers, while it was lower in patients with gastric cancer. Survivors with low rates of eating three meals a day, high skipping breakfast, increased eating-out rate, and no nutritional learning opportunity displayed higher MetS prevalence. Additionally, cancer survivors who had more strength and leisure activities had a lower OR of MetS.

Background: In patients with axial spondyloarthritis (AxSpA), we have reported that higher inflammatory burden as reflected by a longer disease duration, delay in diagnosis and higher erythrocyte sedimentation rate (ESR) levels were predictors associated with incident hypertension after adjusting for traditional cardiovascular (CV) risk factors (1). Whether this is due to accelerated arterial stiffness progression is worth exploring. Methods: One hundred patients with axSpA who fulfilled the ASAS classification criteria and with active disease (ASDAS [Formula: see text]2.1) were recruited from the out-patient clinic of 6 regional hospitals. All participants will receive a 2-year protocolized treatment aiming to achieve ASDAS low disease activity (LDA) in order to address the effects of treating-to-target (T2T) and vascular outcomes (The Hong Kong AxSpA T2T vascular study). Medical history, medication used, disease activity, serum levels of inflammatory markers, cholesterol and fasting glucose were measured/recorded every 6 months. Brachial-ankle pulse wave velocity (baPWV) and carotid ultrasound were assessed at baseline and yearly. In this interim-analysis, we will focus on baPWV. Results: Ninety-two patients completed the month 12 follow-up. The patients were stratified into two groups based on the duration from symptom onset to diagnosis: less than 2 years (early axSpA group) and 2 years or more (non-early axSpA group). Table 1 summarized the demographic and clinical characteristics of both groups. The baseline baPWV values were comparable between the two groups (1412.4 ± 230.45 and 1325.19 ± 174.75, p > 0.05). However, at Month 12, there was a significant difference in baPWV between the groups (1470.77 ± 233.70 and 1302.09 ± 198.52, p= 0.001) (Figure 2). The early axSpA group showed a decrease of 23.09 cm/s, while the non-early axSpA group exhibited an increase of 59.85 cm/s (p=0.033). A multivariate linear regression analysis was conducted to predict the change in baPWV based on age, gender, early axSpA, use of csDMARDs, and glucocorticoids at baseline. Early axSpA remained the only significant predictor and was associated with a positive effect in reducing baPWV ([Formula: see text]= -82.939; p= 0.033). Conclusion: Early diagnosis may be able to prevent progression of arterial stiffness in patients with axial SpA by lowering the cumulative inflammatory burden before effective suppression of inflammation could be given to the patients.

Background: Axial spondyloarthritis (axSpA) is associated with accelerated atherosclerosis driven by chronic inflammation. Achieving LDA may result in significant benefits in articular disease, little is known about its effect on extra-articular disease, including CVD risk in axSpA. To investigate the effect of achieving Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA) using a protocolized treatment strategy on the progression of subclinical atherosclerosis and arterial stiffness in axial spondyloarthritis (axSpA) patients. Methods: One hundred consecutive AxSpA patients will participate in this 2-year prospective, hospital-based, cohort study. All participants will receive 2 years of tight-control treatment. Treatment will be adjusted according to a standardized protocol every 3-6 monthly aiming at ASDAS LDA (ASDAS

Traditional video compression technology based on pixel correlation has limited performance improvement space, semantic compression has become the new direction of video compression coding, and video image reconstruction is the key link of semantic compression coding.First, the video image reconstruction methods for traditional coding optimization were introduced, including how to use deep learning to improve prediction accuracy and enhance reconstruction quality with super-resolution techniques.Second, the video image reconstruction methods based on variational auto-encoders, generative adversarial networks, autoregressive models and transformer models were discussed emphatically.Then, the models were classified according to different semantic representations of images.The advantages, disadvantages, and applicable scenarios of various methods were compared.Finally, the existing problems of video image reconstruction were summarized, and the further research directions were prospected.

Abstract Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the intestine, including Crohn’s disease (CD) and ulcerative colitis (UC), whose etiology and pathogenesis have not been fully understood. Due to its prolonged course and chronic recurrence, IBD imposes a heavy economic burden and psychological stress on patients. Traditional Chinese Herbal Medicine has unique advantages in IBD treatment because of its symptomatic treatment. However, the advantages of the Chinese Herbal Medicine Formula (CHMF) have rarely been discussed. In recent years, many scholars have conducted fundamental studies on CHMF to delay IBD from different perspectives and found that CHMF may help maintain intestinal integrity, reduce inflammation, and decrease oxidative stress, thus playing a positive role in the treatment of IBD. Therefore, this review focuses on the mechanisms associated with CHMF in IBD treatment. CHMF has apparent advantages. In addition to the exact composition and controlled quality of modern drugs, it also has multi-component and multi-target synergistic effects. CHMF has good prospects in the treatment of IBD, but its multi-agent composition and wide range of targets exacerbate the difficulty of studying its treatment of IBD. Future research on CHMF-related mechanisms is needed to achieve better efficacy.

Abstract Prokaryotic expression systems are widely used to produce many types of biologics because of their extreme conveniences and unmatchable cost. However, production of recombinant human ferritin light chain (rhFTL) protein is largely restrained because its expression in Escherichia coli tends to form inclusion bodies (IBs). In this study, a prokaryotic expression vector (FTL‐pBV220) harboring the rhFTL gene was constructed using a pBV220 plasmid. The tag‐free rhFTL was highly expressed and almost entirely converted to soluble form, and thus the rhFTL was successfully self‐assembled into uniform nanoparticles in E. coli. To establish a simplified downstream process, a precipitation procedure based on the optimized incubation temperature, pH condition, and ionic strength was developed to remove impurities from the crude lysate supernatant. The rhFTL retained in the clarified supernatant was subsequently purified in a single step using Capto Butyl column resulting in a considerable recovery and high purity. The purified rhFTL was characterized and verified by mass spectrometry and spectral and morphological analyses. The results revealed that rhFTL exhibited highly ordered and fairly compact structures and the spherical structures were preserved.

Abstract Metallic zinc (Zn) is one of the most attractive multivalent-metal anode materials in post-lithium batteries because of its high abundance, low cost and high theoretical capacity. However, it usually suffers from large voltage polarization, low Coulombic efficiency and high propensity for dendritic failure during Zn stripping/plating, hindering the practical application in aqueous rechargeable zinc-metal batteries (AR-ZMBs). Here we demonstrate that anionic surfactant-assisted in situ surface alloying of Cu and Zn remarkably improves Zn reversibility of 3D nanoporous Zn electrodes for potential use as high-performance AR-ZMB anode materials. As a result of the zincophilic Zn x Cu y alloy shell guiding uniform Zn deposition with a zero nucleation overpotential and facilitating Zn stripping via the Zn x Cu y /Zn galvanic couples, the self-supported nanoporous Zn x Cu y /Zn electrodes exhibit superior dendrite-free Zn stripping/plating behaviors in ambient aqueous electrolyte, with ultralow polarizations under current densities up to 50 mA cm‒2, exceptional stability for 1900 h and high Zn utilization. This enables AR-ZMB full cells constructed with nanoporous Zn x Cu y /Zn anode and K z MnO2 cathode to achieve specific energy of as high as ~ 430 Wh kg‒1 with ~ 99.8% Coulombic efficiency, and retain ~ 86% after long-term cycles for > 700 h.

BackgroundThe World Health Organization has proposed to eliminate hepatitis C by 2030, yet there is still a large gap to the goal. Screening for hepatitis C is cost-effective and efficient in medical institutions. The aim of this study was to identify the key populations for HCV antibody screening in hospital characterized by infectious diseases, and provide estimates of the proportion of HCV-infected persons in the Beijing Ditan hospital completing each step along a proposed HCV treatment cascade.MethodsA total of 105,112 patients who underwent HCV antibody testing in Beijing Ditan hospital between 2017 and 2020 were included in this study. HCV antibody and HCV RNA positivity rate were calculated and compared by chi-square test.ResultsThe positivity rate of HCV antibody was 6.78%. The HCV antibody positivity rate and the proportion of positive patients showed an upward trend along with age in the five groups between 10–59 years. In the contrary, a decreasing trend was observed in the three groups above 60 years. Patients with positive HCV antibody were mainly from the Liver Disease Center (36.53%), the Department of Integrative Medicine (16.10%), the Department of Infectious Diseases (15.93%) and the Department of Obstetrics and Gynecology (9.44%). Among HCV antibody positive patients, 6,129 (85.95%) underwent further HCV RNA testing, of whom 2097 were HCV RNA positive, the positivity rate was 34.21%. Of the patients who were HCV RNA positive, 64.33% did not continue with HCV RNA testing. The cure rate for HCV antibody positive patients was 64.98%. Besides, there was a significant positive correlation between HCV RNA positivity rate and HCV antibody level (r = 0.992, P < 0.001). The detection rate of HCV antibody among inpatients showed an upward trend (Z = 5.567, P < 0.001), while the positivity rate showed a downward trend (Z = 2.2926, P = 0.0219).ConclusionsWe found that even in hospitals characterized by infectious diseases, a large proportion of patients did not complete each step along a proposed HCV treatment cascade. Besides, we identified key populations for HCV antibody screening, namely: (1) patients over 40 years of age, especially those aged 50–59 years; (2) the Department of Infectious Diseases and the Department of Obstetrics and Gynecology patients. In addition, HCV RNA testing was highly recommended for patients with HCV antibody levels above 8 S/CO.

This study developed a snowfall detection algorithm over ocean, sea ice, and coast for the advanced technology microwave sounder (ATMS) onboard both NPP and NOAA-20 satellites. The detection algorithm was trained from collocated observations between ATMS-NPP and CloudSat cloud profiling radar (CPR) snowfall product. Both brightness temperature (TB) variables and global forecast system (GFS) output variables are evaluated for snowfall detection in this algorithm. Results show that combining TB variables and GFS variables provide the optimal snowfall detection performance. The Heidke skill score (HSS) values are about 0.56 over all three surface types, and the probability of detection (POD) values are 0.76, 0.70, and 0.72 over ocean, sea ice, and coast, respectively. The importance of the GFS variables differs greatly among these three surface types. The detection algorithm primarily depends on TB variables over ocean and HSS only increased by 0.05 by adding GFS variables. In contrast, GFS variables are critically important to snowfall detection over sea ice and coastal regions. Without GFS variables, the HSS values over both sea ice and coastal regions decrease sharply from about 0.56 to about 0.40. Over ocean, we also developed a regional snowfall detection model in each 10° grid box, which greatly outperform the global detection model over certain regions (e.g., sea of Okhotsk and Labrador Sea). Case studies and validation against NOAA-20 observations showed that the snowfall detection algorithm performs well, which will benefit coastal communities by providing information on snowstorms offshore before they transition to land.

Aqueous Al-ion batteries are attractive post-lithium battery technologies. Here Al-Cu alloy lamellar heterostructures with periodic galvanic couplings are reported as efficient anode active material to produce high-energy aqueous Al-ion batteries.

The interaction of viruses with hosts is complex, especially so with the antiviral immune systems of hosts, and the underlying mechanisms remain perplexing. Infection with SARS-CoV-2 may result in cytokine syndrome in the later stages, reflecting the activation of the antiviral immune response. However, viruses also encode molecules to negatively regulate the antiviral immune systems of hosts to achieve immune evasion and benefit viral replication during the early stage of infection. It has been observed that the papain-like protease (PLP) encoded by coronavirus could negatively regulate the host’s IFNβ innate immunity. In this study, we first found that eight inflammasome-related genes were downregulated in CD14+ monocytes from COVID-19 patients. Subsequently, we observed that SARS-CoV-2 PLP negatively regulated the NLRP3 inflammasome pathway, inhibited the secretion of IL-1β, and decreased the caspase-1-mediated pyroptosis of human monocytes. The mechanisms for this may arise because PLP coimmunoprecipitates with ASC, reduces ASC ubiquitination, and inhibits ASC oligomerization and the formation of ASC specks. These findings suggest that PLP may inhibit strong immune defenses and provide the maximum advantage for viral replication. This research may allow us to better understand the flex function of CoV-encoding proteases and provide a new perspective on the innate immune responses against SARS-CoV-2 and other viruses.

Coronavirus disease 2019 (COVID-19) is currently a severe threat to global public health, and the immune response to COVID-19 infection has been widely investigated. However, the immune status and microecological changes in the respiratory systems of patients with COVID-19 after recovery have rarely been considered. We selected 72 patients with severe COVID-19 infection, 57 recovered from COVID-19 infection, and 65 with non-COVID-19 pneumonia, for metatranscriptomic sequencing and bioinformatics analysis. Accordingly, the differentially expressed genes between the infected and other groups were enriched in the chemokine signaling pathway, NOD-like receptor signaling pathway, phagosome, TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, and C-type lectin receptor signaling pathway. We speculate that IL17RD, CD74, and TNFSF15 may serve as disease biomarkers in COVID-19. Additionally, principal coordinate analysis revealed significant differences between groups. In particular, frequent co-infections with the genera Streptococcus, Veillonella, Gemella, and Neisseria, among others, were found in COVID-19 patients. Moreover, the random forest prediction model with differential genes showed a mean area under the curve (AUC) of 0.77, and KCNK12, IL17RD, LOC100507412, PTPRT, MYO15A, MPDZ, FLRT2, SPEG, SERPINB3, and KNDC1 were identified as the most important genes distinguishing the infected group from the recovered group. Agrobacterium tumefaciens, Klebsiella michiganensis, Acinetobacter pittii, Bacillus sp. FJAT.14266, Brevundimonas naejangsanensis, Pseudopropionibacterium propionicum, Priestia megaterium, Dialister pneumosintes, Veillonella rodentium, and Pseudomonas protegens were selected as candidate microbial markers for monitoring the recovery of COVID patients. These results will facilitate the diagnosis, treatment, and prognosis of COVID patients recovering from severe illness.

BackgroundThe mechanism of cuproptosis has recently been reported in lipoylated proteins of the tricarboxylic acid (TCA) cycle. Besides, the role of copper was previously recognized in cancer progression. We evaluated the prognostic value of cuproptosis-related gene expression in hepatocellular carcinoma (HCC).MethodsRemarkable genes were selected both in differential expression analysis and Kaplan-Meier survival analysis from ninety-six cuproptosis-related genes using The Cancer Genome Atlas (TCGA) database. The relationships between clinical characteristics and gene expression were performed with Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression. Clinicopathologic factors correlated with overall survival in HCCs conducting univariate and multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA) databases were utilized to verify the results. Furthermore, Gene Set Enrichment Analysis (GSEA) identified the potential key pathways that dominate cuproptosis in HCC.ResultsElevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 and NDOR1 expression, as well as declined AOC1, FDX1, MT-CO1, and ACO1 expression were significantly emerged in HCC tumor tissues and were significantly associated with HCCs poor survival. The expressions of screened cuproptosis-related genes were prominently related to clinical features. GSEA analysis reported many key signaling pathways (such as natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch signaling pathway, ErbB signaling pathway, and metabolism of xenobiotics by cytochrome p450) were differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression.ConclusionsThe twenty cuproptosis-related genes might be utilized as new candidate prognostic biomarkers for HCC.

Chiral aliphatic amine and alcohol derivatives are difficult to access due to the challenge to differentiate between spatially and electronically similar alkyl groups. Here the authors show a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent enantioselectivity.

Cancer metastasis is the leading cause of death in patients, here, the authors show disrupting tumor vasculature could recruit and activate anti-PD-L1 engineered platelet at metastatic tumor sites to block the PD-1/PD-L1 crosstalk and enhance the anticancer immunotherapy.

BackgroundWhether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA.MethodSeventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis.Results29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP− group: 564.6 [329.3–910.5] ng/ml; CP+ group: 721.3 [329.3–910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037).ConclusionSerum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

Inflammatory bowel disease (IBD) is a rare, recurrent, and intractable inflammation obstruction of the stomach tract, usually accompanied by inflammation of cell proliferation and inflammation of the colon and carries a particular cause of inflammation. The clinical use of drugs in western countries affects IBD treatment, but various adverse effects and high prices limit their application. For these reasons, Traditional Chinese Medicine (TCM) is more advantageous in treating IBD. This paper reviews the mechanism and research status of TCM and natural products in IBD treatment by analyzing the relevant literature to provide a scientific and theoretical basis for IBD treatment.

Abstract New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Dry age-related macular degeneration(ARMD)is a degenerative fundus disease whose pathogenesis is not yet fully clear. Dry ARMD with macular pigmentation disorder, drusen and geographic atrophy as main manifestations can lead to irreversible loss of central vision. It's reported that immune and inflammatory reactions play a key role in the development of dry ARMD, in which complement system, pattern recognition receptors, inflammasomes, and various cytokines in immune molecules are closely related to the occurrence of dry ARMD. In this paper, the latest researches on these immune molecules and dry ARMD will be reviewed.

Hepatocyte 12-hour rhythms have a role in cellular stress and metabolic functions. Here, the authors demonstrate disrupting the 12-hour clock through deletion of XBP1 is associated with the development of NAFLD as well as disruption of phospholipid composition and the maintenance of lipid homeostasis.

Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). Here, the authors use ratiometrically designed nanoparticles to codeliver the CDK4/6 inhibitor palbociclib and the autophagy inhibitor hydroxychloroquine, and show their synergistic therapeutic effects in mouse model of PDAC.

Summary: The 12-h clock coordinates lipid homeostasis, energy metabolism, and stress rhythms via the transcriptional regulator XBP1. However, the biochemical and physiological bases for integrated control of the 12-h clock and diverse metabolic pathways remain unclear. Here, we show that steroid receptor coactivator SRC-3 coactivates XBP1 transcription and regulates hepatic 12-h cistrome and gene rhythmicity. Mice lacking SRC-3 show abnormal 12-h rhythms in hepatic transcription, metabolic functions, systemic energetics, and rate-limiting lipid metabolic processes, including triglyceride, phospholipid, and cardiolipin pathways. Notably, 12-h clock coactivation is not only preserved, with its cistromic activation priming ahead of the zeitgeber cue of light, but concomitant with rhythmic remodeling in the absence of food. These findings reveal that SRC-3 integrates the mammalian 12-h clock, energy metabolism, and membrane and lipid homeostasis and demonstrates a role for the 12-h clock machinery as an active transcriptional mechanism in anticipating physiological and metabolic energy needs and stresses.

Cardiac rehabilitation (CR) is a system that comprehensively manages risk factors to reduce the recurrence rate after cardiovascular disease treatment. This study compared the effects of home-based low-frequency CR (1–2 times/week) and center-based high-frequency CR (3–5 times/week) for 12 weeks. This study was conducted as an observational case-control study. Ninety women, ages 45 to 60, who underwent coronary artery stenting were enrolled. Measurement variables were waist circumference, body mass index (BMI), blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), glucose, VO2 peak, body composition, and quality of life. Significant changes were observed in systolic BP, TC, LDLC, TG, VO2 peak, exercise duration, and quality of life in both groups. However, BMI, waist circumference, body fat percentage, HDLC, and blood glucose only exhibited significant changes with HFT. The interaction effects according to time and group were as follows: systolic BP, waist circumference, body fat, BMI, HDLC, and glucose (p < 0.05). Therefore, in CR participants, HFT improved more than LFT on obesity factors, HDLC, and glucose change. As well as center-based HFT, home-based LFT also improved risk factors for cardiovascular disease, fitness, and quality of life. For female patients who have difficulty visiting the CR center frequently, home-based LFT may be a CR program that can be presented as an alternative.

Rhodococcus equi is a zoonotic pathogen that can cause fatal disease in patients who are immunocompromised. At present, the epidemiology and pathogenic mechanisms of R. equi infection are not clear. This study characterized the genomes of 53 R. equi strains from different sources. Pan-genome analysis showed that all R. equi strains contained 11481 pan genes, including 3690 core genes and 602 ~ 1079 accessory genes. Functional annotation of pan genome focused on the genes related to basic lifestyle, such as the storage and expression of metabolic and genetic information. Phylogenetic analysis based on pan-genome showed that the R. equi strains were clustered into six clades, which was not directly related to the isolation location and host source. Also, a total of 84 virulence genes were predicted in 53 R. equi strains. These virulence factors can be divided into 20 categories related to substance metabolism, secreted protein and immune escape. Meanwhile, six antibiotic resistance genes (RbpA, tetA (33), erm (46), sul1, qacEdelta 1 and aadA9) were detected, and all strains carried RbpA related to rifamycin resistance. In addition, 28 plasmids were found in the 53 R. equi strains, belonging to Type-A (n = 14), Type-B (n = 8) and Type-N (n = 6), respectively. The genetic structures of the same type of plasmid were highly similar. In conclusion, R. equi strains show different genomic characteristics, virulence-related genes, potential drug resistance and virulence plasmid structures, which may be conducive to the evolution of its pathogenesis.