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Abstract It may be difficult for existing methods to make full use of the correlation and complementarity of various kinds of information when processing multi-source information. In order to accurately perceive the security situation of distribution automation and ensure the safe and stable operation of distribution network, the multi-source information fusion distribution automation security situation awareness technology based on risk transmission path is studied. Based on the risk transmission path, the distribution automation security situational awareness factors are analyzed, and the main factors affecting the distribution automation security situation are divided into two dimensions: internal source and external source, and eight main awareness factors; Different types of sensors are set in the main areas of security situational awareness factors to collect data of different awareness factors. Using ant colony algorithm to optimize DS evidence fusion method, data with different perception factors are fused, and data fusion results with different perception factors are obtained. The distribution automation security situational awareness model is constructed, and the security situational awareness results are obtained based on the data fusion results of the awareness factors. If the results are higher than the set threshold, the abnormal signal can be output to determine the area where the distribution automation abnormal equipment is located. The experimental results show that the multi-source data fusion effect of this method is good, and it can accurately perceive the security status of different nodes of the experimental object at different time nodes.

Abstract Background Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Materials and methods Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques. Results In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P

Taking amphibians as island models, we examined the effects of interspecific interaction on the diversity and stability of microbial ecological. As skin area increased, the diversity and stability of skin microbes decreased, but the strength of negative interactions increased significantly. In contrast, as gut area increased, the diversity and stability of gut microbes increased, but the strength of interactions remained constant. These results indicate that microbial interactions are affected by habitat properties. When living in fluctuating environments without strong filtering, microorganisms can enhance their negative interactions with other taxa by changing the pH of their surroundings. In contrast, the pH of the gut is relatively stable, and colonized microorganisms cannot alter the gut pH and inhibit other colonizers. This study demonstrates that in the field of microbiology, diversity and stability are predominantly influenced by the intensity of interspecies interactions. The findings in this study deepen our understanding of microbial diversity and stability and provide a mechanistic link between species interactions, biodiversity, and stability in microbial ecosystems.

Abstract Super‐resolution imaging techniques, such as structured illumination microscopy (SIM), have enabled researchers to obtain nanoscale organelle‐level outputs in living systems, but they impose additional stringent requirements on fluorescence probes. However, high‐performance, custom‐designed SIM probes that can explain underlying biological processes remain unavailable. Herein, a customizable engineering toolkit is developed for the facile assembly of SIM probes suitable for subcellular component detection. This toolkit is used to customize a fluorescent molecule, CPC (coumarin–phenylhydrazine–carboxyl), capable of simultaneously monitoring peroxynitrite (ONOO−) and polarity distribution in mitochondria and lipid droplets (LDs), respectively, through functional ON–OFF mechanisms. The customized CPC molecule demonstrated excellent imaging capabilities under SIM, enabled the successful localization of multiple organelles, and reliably tracked the distribution of different components, thus facilitating the study of the interplay between organelles. Using CPC, the physical transition of intracellular LDs is demonstrated from heterogeneity to homogeneity. This was specifically observed during ferroptosis where the polarity of the LDs increased and their morphology became more contracted. Furthermore, the loss of LDs functionality could not counteract the accumulation of ONOO− within the mitochondria, leading to the decoupling of mitochondrial LDs during ferroptosis. These results confirmed the potential mechanism of LDs dysfunction and decoupling triggered via cumulative mitochondrial oxidative stress during ferroptosis. To summarize, this toolkit will be a powerful tool for examining subtle variations among components during the interplay between different organelles, thus offering novel avenues for understanding and treating related diseases.

Abstract Introduction Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. Methods First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. Results SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. Conclusions SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Abstract In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

BackgroundOsteoarthritis (OA) holds the distinction of being the most widespread musculoskeletal disorder. Any disruptions in the integrity of the articular cartilage can result in joint malfunction, discomfort, and impaired physical functioning. Increasing evidence indicates the negative impacts of caffeine intake on hyaline cartilage. The primary objective of this study was to delve deeper into understanding the potential link between the consumption of caffeine and the risk of developing OA.MethodsIn this study, we constructed logistic regression models to evaluate the correlation between caffeine consumption and the risk of osteoarthritis using data from the National Health and Nutrition Examination Survey. Following that, we utilized genome-wide association studies to conduct a Mendelian randomization (MR) analysis investigating the association between coffee consumption and the likelihood of developing knee OA. We employed various statistical methods, including inverse variance weighting (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression, to ensure comprehensive analysis and robust conclusions. To evaluate heterogeneity and the potential impact of pleiotropy, we conducted several statistical tests, including Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR Steiger test.ResultsThe weighted multivariate logistic regression analysis showed that the relationship between high caffeine intake (95–206 and ≥206 mg/day) and OA prevalence remained significantly high even after adjusting for covariates using the lowest caffeine intake (< 11 mg/day) as reference: Model 1—OR (95% Cl) = 1.365 (1.18–1.58) and 1.59 (1.38–1.83); Model 2—OR (95% Cl) = 1.21 (1.04–1.42) and 1.44 (1.23–1.68); and Model 3—OR (95% Cl) = 1.19 (1.01–1.40) and 1.30 (1.10–1.52), respectively (p < 0.05). The findings from the fixed effects inverse variance weighted (IVW) analysis revealed a statistically significant link between coffee intake and the likelihood of developing knee osteoarthritis: OR = 1.94; 95% confidence interval (Cl) =1.471–2.517; (p < 0.001). Consistent findings were obtained across various other methods, including MR-Egger regression, weighted median, weighted mode, and simple mode analyses.ConclusionOur study showed a positive correlation between OA prevalence and high caffeine intake (≥95 mg/day).

Abstract Highly interconnected production network exists in one economy, and it is crucial to investigate how and why supply-side shocks spread across industries via the production network and cause systemic risks in the real sector. Based on input-output framework, this paper designed a model to simulate the propagation of risk spillovers along the production network given supply-side shocks. This paper defined the systemically important industries (SIIs) and systemically vulnerable industries (SVIs) according to the degree and direction of risk spillovers. Simulation results show that risk spillovers spread among industries via the production network, leading to systemic risk in the real sector. This paper also classified the important risk spillover paths “SVIs → SIIs → SVIs” in the model for risk regulation and prevention and identified 75 risk spillover paths and 9 closed-loop paths in 2018. Furthermore, key factors of systemic importance (vulnerability) included input-output relationships and production network centrality. This paper provides a scientific basis to strengthen the risk supervision of the real sector based on the supply chain.

Intervertebral disc degeneration (IVDD) is a common and frequent disease in orthopedics, which seriously affects the quality of life of patients. Endoplasmic reticulum stress (ERS)-regulated autophagy and apoptosis play an important role in nucleus pulposus (NP) cells in IVDD. Hypoxia and serum deprivation were used to induce NP cells. Cell counting kit-8 (CCK-8) assay was used to detect cell activity and immunofluorescence (IF) was applied for the appraisement of glucose regulated protein 78 (GRP78) and green fluorescent protein (GFP)-light chain 3 (LC3). Cell apoptosis was detected by flow cytometry and the expression of LC3II/I was detected by western blot. NP cells under hypoxia and serum deprivation were induced by lipopolysaccharide (LPS), and intervened by ERS inhibitor (4-phenylbutyric acid, 4-PBA) and activator (Thapsigargin, TP). Then, above functional experiments were conducted again and western blot was employed for the evaluation of autophagy-, apoptosis and ERS-related proteins. Finally, NP cells under hypoxia and serum deprivation were stimulated by LPS and intervened using apoptosis inhibitor z-Val-Ala-DL-Asp-fluoromethyl ketone (Z-VAD-FMK) and autophagy inhibitor 3-methyladenine (3-MA). CCK-8 assay, IF, flow cytometry and western blot were performed again. Besides, the levels of inflammatory cytokines were measured with enzyme-linked immunosorbent assay (ELISA) and the protein expressions of programmed death markers were estimated with western blot. It showed that serum deprivation induces autophagy and apoptosis. ERS was significantly activated by LPS in hypoxic and serum deprivation environment, and autophagy and apoptosis were significantly promoted. Overall, ERS affects the occurrence and development of IVDD by regulating autophagy, apoptosis and other programmed death.

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in lemon, sweet orange, bitter orange, clementine. Hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory, antioxidant, antitumor and antibacterial potential. Preclinical studies and clinical trials demonstrated therapeutical effects of hesperidin and its aglycone hesperetin in various diseases, such as bone diseases, cardiovascular diseases, neurological diseases, respiratory diseases, digestive diseases, urinary tract diseases. This review provides a comprehensive overview of the biological activities of hesperidin and hesperetin, their therapeutic potential in various diseases and their associated molecular mechanisms. This article also discusses future considerations for the clinical applications of hesperidin and hesperetin.

Abstract Background Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has limitations in staging hepatocellular carcinoma (HCC). The recently introduced 18F-labeled fibroblast-activation protein inhibitor (FAPI) has shown promising prospects in detection of HCC lesions. This study aimed to investigate the initial staging and restaging performance of 18F-FAPI PET/CT compared to 18F-FDG PET/CT in HCC. Methods This prospective study enrolled histologically confirmed HCC patients from March 2021 to September 2022. All patients were examined with 18F-FDG PET/CT and 18F-FAPI PET/CT within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. Results A total of 67 patients (57 men; median age, 57 [range, 32–83] years old) were included. 18F-FAPI PET showed higher SUVmax and TBR values than 18F-FDG PET in the intrahepatic lesions (SUVmax: 6.7 vs. 4.3, P 0.05]. 18F-FAPI PET/CT detected primary tumors in 16 patients with negative 18F-FDG, upgraded T-stages in 12 patients and identified 4 true positive findings for local recurrence than 18F-FDG PET, leading to planning therapy changes in 47.8% (32/67) of patients. Conclusions 18F-FAPI PET/CT identified more primary lesions, lymph node metastases than 18F-FDG PET/CT in HCC, which is helpful to improve the clinical management of HCC patients. Trial registration Clinical Trials, NCT05485792 . Registered 1 August 2022, Retrospectively registered.

Abstract Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A–SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition.

Due to external factors such as political influences, specific events and sentiment information, stock prices exhibit randomness, high volatility and non-linear characteristics, making accurate predictions of future stock prices based solely on historical stock price data difficult. Consequently, data fusion methods have been increasingly applied to stock price prediction to extract comprehensive stock-related information by integrating multi-source heterogeneous stock data and fusing multiple decision results. Although data fusion plays a crucial role in stock price prediction, its application in this field lacks comprehensive and systematic summaries. Therefore, this paper explores the theoretical models used in each level of data fusion (data-level, feature-level and decision-level fusion) to review the development of stock price prediction from a data fusion perspective and provide an overall view. The research indicates that data fusion methods have been widely and effectively used in the field of stock price prediction. Additionally, future directions are proposed. For better performance of data fusion in the field of stock price prediction, future work can broaden the scope of stock-related data types used and explore new algorithms such as natural language processing (NLP) and generative adversarial networks (GAN) for text information processing.

Objectives The negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study is to explore whether the prevalence of non-alcoholic fatty liver disease (NAFLD) in former smokers differs from the prevalence in current smokers.Design Systematic review and meta-analysis.Data sources Four databases, that is, PubMed, Web of Science, Journal@Ovid and Scopus were searched from inception to 31 January 2023.Eligibility criteria Population-based cross-sectional studies, including the baseline data of cohort studies with identified NAFLD diagnostic methods, and smoking status (current smoker or former smoker) of participants were included.Data extraction and synthesis Two reviewers independently extracted the data including cigarette smoking status, country/region of studies, NAFLD diagnostic methods, sex, the average age and body mass index (BMI) of NAFLD participants and assessed the risk of bias with Agency for Healthcare Research and Quality (AHRQ) methodology checklist. Risk ratio (RR) of NAFLD prevalence in former smokers was pooled using the random-effects model.Results 28 studies involving 4 465 862 participants were included. Compared with current smokers, the RR of overall NAFLD prevalence in former smokers was 1.13 (95% CI: 1.08 to 1.19, prediction interval: 0.92–1.39). This result persisted after adjustment for diagnostic methods, country/region, sex, age and BMI. Sensitivity analysis and risk of bias assessment indicated a stable conclusion.Conclusions NAFLD prevalence in former smokers was at least not lower than that in current smokers and was partially related to increased BMI after smoking cessation, indicating that smoking cessation was possibly not a protective factor against NAFLD. Although the meta-analysis based on cross-sectional studies cannot conclude the causal relationships between smoking cessation and NAFLD onset, the potential onset of NAFLD associated with smoking cessation should be highlighted.PROSPERO registration number CRD42023394944.

Abstract Background Type 2 diabetes mellitus (T2DM) with obesity is a glycolipid metabolism disorder, which makes hypoglycaemic treatment more complex and increases the proportion of multidrug combinations. In addition, patients are more prone to adverse reactions and gradually lose compliance with treatment. Previous clinical trials have demonstrated that Daixie Decoction granules (DDG) can reduce body weight and blood lipids and improve the quality of life of T2DM with obesity. But there are a lack of further evaluations for the efficacy and safety of DDG combined with metformin. Methods/design The study is designed as a multicentre, randomized, double-blind, placebo-controlled clinical trial. Participants who meet the Nathrow criteria will be randomly assigned to the intervention group and control group (n 1 = n 2 = 133). Based on a unified diet control and exercise therapy, the intervention group will be treated with DDG and metformin, and the control group will be treated with DDG placebo and metformin. All subjects will receive a 6-month treatment followed by a 6-month follow-up. Effective rate of a 1% decrease in HbA1c and 3% decrease in body weight will serve as the primary outcome. The secondary outcome include fasting plasma glucose, blood lipids, C-peptides, insulin, inflammatory factors, insulin resistance index (HOMA-IR) and the subcutaneous and visceral fat content in the upper abdomen measured by MRI. Blood routine, urine routine, stool routine, liver and kidney function, EKG and other safety indicators and major adverse reactions were monitored during total treatment and follow-up time. Discussion We aimed to determine the efficacy and safety of DDG combined with metformin for the treatment of T2DM patients with obesity. Trial registration Trial registration: ChiCTR, ChiCTR2000036290. Registered 22 August 2014, http://www.chictr.org.cn/showprojen.aspx? proj=59001

Antarctic krill tropomyosin (AkTM) has been shown in mice to cause IgE-mediated food allergy. The objective of this work was to investigate the role of Notch signaling in AkTM-sensitized mice, as well as to determine the changes in gut microbiota composition and short-chain fatty acids (SCFAs) in the allergic mice. An AkTM-induced food allergy mouse model was built and N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) was used as an γ-secretase inhibitor to inhibit the activation of Notch signaling. Food allergy indices, some key transcription factors, histologic alterations in the small intestine, and changes in gut microbiota composition were examined. The results showed that DAPT inhibited Notch signaling, which reduced AkTM-specific IgE, suppressed mast cell degranulation, decreased IL-4 but increased IFN-γ production, and alleviated allergic symptoms. Quantitative real-time PCR and Western blotting analyses revealed that expressions of Hes-1, Gata3, and IL-4 were down-regulated after DAPT treatment, accompanied by increases in T-bet and IFN-γ, indicating that Notch signaling was active in AkTM-sensitized mice and blocking it could reverse the Th1/Th2 imbalance. Expressions of key transcription factors revealed that Notch signaling could promote Th2 cell differentiation in sensitized mice. Furthermore, 16S rRNA sequencing results revealed that AkTM could alter the diversity and composition of gut microbiota in mice, leading to increases in inflammation-inducing bacteria such as Enterococcus and Escherichia-Shigella. Correlation analysis indicated that reduced SCFA concentrations in AkTM-allergic mice may be related to decreases in certain SCFA-producing bacteria, such as Clostridia_UCG-014. The changes in gut microbiota and SCFAs could be partially restored by DAPT treatment. Our findings showed that inhibiting Notch signaling could alleviate AkTM-induced food allergy by correcting Th1/Th2 imbalance and modulating the gut microbiota.

Summary: Comprehensive multiplatform analysis of Luminal B breast cancer (LBBC) specimens identifies two molecularly distinct, clinically relevant subtypes: Cluster A associated with cell cycle and metabolic signaling and Cluster B with predominant epithelial mesenchymal transition (EMT) and immune response pathways. Whole-exome sequencing identified significantly mutated genes including TP53, PIK3CA, ERBB2, and GATA3 with recurrent somatic mutations. Alterations in DNA methylation or transcriptomic regulation in genes (FN1, ESR1, CCND1, and YAP1) result in tumor microenvironment reprogramming. Integrated analysis revealed enriched biological pathways and unexplored druggable targets (cancer-testis antigens, metabolic enzymes, kinases, and transcription regulators). A systematic comparison between mRNA and protein displayed emerging expression patterns of key therapeutic targets (CD274, YAP1, AKT1, and CDH1). A potential ceRNA network was developed with a significantly different prognosis between the two subtypes. This integrated analysis reveals a complex molecular landscape of LBBC and provides the utility of targets and signaling pathways for precision medicine.

Abstract Background Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE. Methods Pilocarpine was used to induced SE in mice. SE‐generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE‐induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics. Results The results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety‐like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D‐fructose‐1,6‐bisphosphate. Conclusion To the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy‐associated psychiatric and cognitive disorders.

Amphibians are known to have an abundance of microorganisms colonizing their skin, and these symbionts often protect the host from disease. There are now many comprehensive studies on amphibian skin microbes, but the interspecific and intraspecific abundance distributions (or abundance heterogeneity) of amphibian skin microbes remain unclear. Furthermore, we have a very limited understanding of how the abundance and heterogeneity of microbial communities relate to the body size (or more specifically, skin surface area) of amphibian hosts. In this study, we evaluated the interspecific and intraspecific abundance distribution patterns of amphibian skin microbes and evaluated whether the symbiotic skin microbes of different anuran species share a fundamental heterogeneity scaling parameter. If scaling invariance exists, we hypothesize that a fundamental heterogeneity scaling value also exists. A total of 358 specimens of 10 amphibian host species were collected, and we used Type-I and III Taylor’s power law expansions (TPLE) to assess amphibian skin microbial heterogeneity at the community and mixed-species population levels, respectively. The obtained results showed that, at the community scale, a high aggregation of the microbial abundance distribution on the skin barely changed with host size. In a mixed-species population (i.e., a community context), the abundance distribution pattern of mixed microbial species populations also does not change with host size and always remains highly aggregated. These findings suggest that while amphibian skin microbiomes located in different hosts may have different environmental conditions, they share a fundamental heterogeneity scaling parameter, and thus, scale invariance exists. Finally, we found that microhabitat area provided by the host skin is vital to the stability of the symbiotic microbial community.

Abstract Background To monitor dypsnea and mortality at 5 and 10 years, respectively, after surgical treatment of tuberculosis-destroyed lung (TDL) patients. Methods TDL patients treated surgically at Beijing Chest Hospital from November 2007 to June 2019 were monitored in this observational study. Follow-up assessments of respiratory function indicators and survival conducted 5 and 10 years post-surgery led to patient grouping based on mMRC score into a dyspnea group (mMRC ≥ 1) and a non-dyspnea group (mMRC = 0). Cox regression analysis detected effects of patient demographics, clinical characteristics, surgical factors and respiratory function on 5 year post-surgical survival. Results By study completion (June 30, 2020), 32 of 104 patients were lost and 72 completed follow-up for a study total of 258.9 person-years. 45 patients (62.5%, 45/72) had mMRC scores of 0, while 12 (16.7%, 12/72), 21 (36.2%, 21/58) and 27 (60.0%, 27/45) patients exhibited dyspnea by 1, 3 and 5 years post-surgery, respectively. Low lung carbon monoxide diffusion score (DLCO% pred) and scoliosis contributed to dyspnea occurrence. Conclusions Most TDL patients lacked subjective dyspnea signs post-surgery, while dyspnea rates increased with time. Preoperative low lung diffusion function and Scoliosis were associated with factors for postoperative dyspnea. Surgical treatment increased TDL patient survival overall.

Abstract Background Poor in vivo targeting of tumors by chemotherapeutic drugs reduces their anti-cancer efficacy in the clinic. The discovery of over-expressed components on the tumor cell surface and their specific ligands provide a basis for targeting tumor cells. However, the differences in the expression levels of these receptors on the tumor cell surface limit the clinical application of anti-tumor preparations modified by a single ligand. Meanwhile, toxicity of chemotherapeutic drugs leads to poor tolerance to anti-tumor therapy. The discovery of natural active products antagonizing these toxic side effects offers an avenue for relieving cancer patients’ pain during the treatment process. Since the advent of nanotechnology, interventions, such as loading appropriate drug combinations into nano-sized carriers and multiple tumor-targeting functional modifications on the carrier surface to enhance the anti-tumor effect and reduce toxic and side effects, have been widely used for treating tumors. Results Nanocarriers containing doxorubicin hydrochloride (DOX) and salvianolic acid A (Sal A) are spherical with a diameter of about 18 nm; the encapsulation efficiency of both DOX and salvianolic acid A is greater than 80%. E-[c(RGDfK)2]/folic acid (FA) co-modification enabled nanostructured lipid carriers (NLC) to efficiently target a variety of tumor cells, including 4T1, MDA-MB-231, MCF-7, and A549 cells in vitro. Compared with other preparations (Sal A solution, NLC-Sal A, DOX solution, DOX injection, Sal A/DOX solution, NLC-DOX, NLC-Sal A/DOX, and E-[c(RGDfK)2]/FA-NLC-Sal A/DOX) in this experiment, the prepared E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had the best anti-tumor effect. Compared with the normal saline group, it had the highest tumor volume inhibition rate (90.72%), the highest tumor weight inhibition rate (83.94%), led to the highest proportion of apoptosis among the tumor cells (61.30%) and the lowest fluorescence intensity of proliferation among the tumor cells (0.0083 ± 0.0011). Moreover, E-[c(RGDfK)2]/FA-NLC-Sal A/DOX had a low level of nephrotoxicity, with a low creatinine (Cre) concentration of 52.58 μmoL/L in the blood of mice, and no abnormalities were seen on pathological examination of the isolated kidneys at the end of the study. Sal A can antagonize the nephrotoxic effect of DOX. Free Sal A reduced the Cre concentration of the free DOX group by 61.64%. In NLC groups, Sal A reduced the Cre concentration of the DOX group by 42.47%. The E-[c(RGDfK)2]/FA modification reduced the side effects of the drug on the kidney, and the Cre concentration was reduced by 46.35% compared with the NLC-Sal A/DOX group. These interventions can potentially improve the tolerance of cancer patients to chemotherapy. Conclusion The E-[c(RGDfK)2]/FA co-modified DOX/Sal A multifunctional nano-drug delivery system has a good therapeutic effect on tumors and low nephrotoxicity and is a promising anti-cancer strategy. Graphical Abstract

Chemo-photothermal/photodynamic synergistic therapy is a new effective cancer treatment method to overcome the limitations of single chemotherapy. However, the limited low photothermal conversion efficiency, the hypoxic tumor microenvironment, and premature leakage of the drug constrain their clinical applications. To address these challenges, an all-in-one biodegradable polydopamine-coated UiO-66 framework nanomedicine (DUPM) was developed to co-deliver the drug doxorubicin hydrochloride (DOX) and the excellent photothermal material MoOx nanoparticles (NPs). The results showed that DUPM exhibited good physicochemical stability and efficiently accumulated tumor tissues under pH-, glutathione-, and NIR-triggered drug release behaviour. Of note, the synthesized MoOx NPs endowed DUPM with self-supporting oxygen production and generated more reactive oxygen species (1O2 and·OH), besides, it induces Mo-mediated redox reaction to deplete excessive glutathione thus relieving tumor hypoxia to enhance PDT, further improving synergistic therapy. Meanwhile, DUPM showed strong absorption in the near-infrared range and high photothermal conversion efficiency at 808 nm (51.50%) to realize photoacoustic imaging-guided diagnosis and treatment of cancer. Compared with monotherapy, the in vivo anti-tumor efficacy results showed that DUMP exerted satisfactory tumor growth inhibition effects (94.43%) with good biocompatibility. This study provides a facile strategy to develop intelligent multifunctional nanoparticles with tumor hypoxia relief for improving synergistic therapy and diagnosis against breast cancer.

Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.

ABSTRACT Unlike species-area relationships (SARs) that have been widely reported for plants and animals on Earth, there is no clear understanding of the SARs for microorganisms. In this study, 358 specimens of 10 amphibian host species collected from the rural Chengdu region of southwest China were selected as island models for evaluating SAR curve shapes and assessing the skin microbiota from different amphibian species. The results showed that skin microbial diversity, measured using Hill’s number, presented significant differences between hosts, but the difference was insignificant between habitat-specific classifications of hosts. As for microbial SARs, other than the classical power-law (PL) model describing an expected steady increase in microbial diversity as sampled skin area increases, two additional trends were observed: (i) microbial diversity first rises and gradually decreases after reaching a maximum accrual diversity (MaxAD) and (ii) microbial diversity decreases and starts to rise after reaching the minimum accrual diversity (MinAD). Among the four SAR statistical models compared, it was consistently found that the models that can describe MaxAD were favorably selected in the highest frequency. Models that can describe MinAD and PL model also performed reasonably well. However, PL had the poorest fitting power, implying the necessity of introducing biologically meaningful complex SAR models in microbial diversity research. In conclusion, through multihost analyses, our study provided compelling evidence that microbial SARs are complex and nonlinear. A variety of ecological mechanisms may be used for explaining these, including, but not limited to, community saturation, small-island effects, or sampling heterogeneity. IMPORTANCE In this study, we investigate species-area relationships (SARs) for skin-borne symbiotic microbes of wildlife hosts. Unlike the traditional SARs for plants and animals, symbiotic microbial SARs were complex. We found that both U-shaped and inverted U-shaped SAR models were widely favored for microbial taxa than the well-known power-law model in different host species. These favored models presented interesting statistical features, including minimal or maximal accrual diversity or inflection point. We provide intuitive derivations of these statistical properties. We showed that different habitat-specific amphibian hosts did not present distinct microbial diversity and skin-related SAR patterns. We predicted that approximately 600 to 1,400 cm2 (in two-dimensional [2D] measurement) or approximately 1,200 to 3 500 cm2 (in 3D measurement) are the skin area threshold range that can allow the emergence of minimal or maximal accrual microbial diversity with high chances. Finally, we list a variety of ecological mechanisms that may be used for explaining the observed nonlinear SAR trends.

Dissolved gas analysis (DGA) in transformer oil, which analyzes its gas content, is valuable for promptly detecting potential faults in oil-immersed transformers. Given the limitations of traditional transformer fault diagnostic methods, such as insufficient gas characteristic components and a high misjudgment rate for transformer faults, this study proposes a transformer fault diagnosis model based on multi-scale approximate entropy and optimized convolutional neural networks (CNNs). This study introduces an improved sparrow search algorithm (ISSA) for optimizing CNN parameters, establishing the ISSA-CNN transformer fault diagnosis model. The dissolved gas components in the transformer oil are analyzed, and the multi-scale approximate entropy of the gas content under different fault modes is calculated. The computed entropy values are then used as feature parameters for the ISSA-CNN model to derive diagnostic results. Experimental data analysis demonstrates that multi-scale approximate entropy effectively characterizes the dissolved gas components in the transformer oil, significantly improving the diagnostic efficiency. Comparative analysis with BPNN, ELM, and CNNs validates the effectiveness and superiority of the proposed ISSA-CNN diagnostic model across various evaluation metrics.

Morphology plays a crucial role in understanding the intricacies of biological forms. Traditional morphometric methods, focusing on one- or two-dimensional geometric levels, often fall short of accurately capturing the three-dimensional (3D) structure of organisms. The advent of 3D scanning techniques has revolutionized the study of organismal morphology, enabling comprehensive and accurate measurements. This study employs a 3D structured light scanning system to analyze the morphological variations in the Chinese toad (Bufo gargarizans Cantor, 1842) along the Yellow River Basin. The 3D digital model obtained from the scan was used to calculate various morphological parameters including body surface area, volume, fractal dimensions, and limb size. The research explores geographic variability patterns and identifies environmental drivers affecting the 3D phenotypic variation of B. gargarizans. Results reveal a bimodal pattern of variation in the toad population, with higher elevations exhibiting smaller body sizes, greater appendage proportions, and more complex body structures. Linear regression analyses highlight the influence of elevation and annual mean temperature on the morphological variation of B. gargarizans, with elevation playing a significant role. This study underscores the significance of 3D morphometric analysis in unraveling the intricacies of organismal morphology and understanding the adaptive strategies of species in diverse environments.

Chronic wounds are a major health challenge that require new treatment strategies. Hydrogels are promising drug delivery systems for chronic wound healing because of their biocompatibility, hydration, and flexibility. However, conventional hydrogels cannot adapt to the dynamic and complex wound environment, which involves low pH, high levels of reactive oxygen species, and specific enzyme expression. Therefore, smart responsive hydrogels that can sense and respond to these stimuli are needed. Crucially, smart responsive hydrogels can modulate drug release and eliminate pathological factors by changing their properties or structures in response to internal or external stimuli, such as pH, enzymes, light, and electricity. These stimuli can also be used to trigger antibacterial responses, angiogenesis, and cell proliferation to enhance wound healing. In this review, we introduce the synthesis and principles of smart responsive hydrogels, describe their design and applications for chronic wound healing, and discuss their future development directions. We hope that this review will inspire the development of smart responsive hydrogels for chronic wound healing.

Abstract Background Protein–protein interaction (PPI) is vital for life processes, disease treatment, and drug discovery. The computational prediction of PPI is relatively inexpensive and efficient when compared to traditional wet-lab experiments. Given a new protein, one may wish to find whether the protein has any PPI relationship with other existing proteins. Current computational PPI prediction methods usually compare the new protein to existing proteins one by one in a pairwise manner. This is time consuming. Results In this work, we propose a more efficient model, called deep hash learning protein-and-protein interaction (DHL-PPI), to predict all-against-all PPI relationships in a database of proteins. First, DHL-PPI encodes a protein sequence into a binary hash code based on deep features extracted from the protein sequences using deep learning techniques. This encoding scheme enables us to turn the PPI discrimination problem into a much simpler searching problem. The binary hash code for a protein sequence can be regarded as a number. Thus, in the pre-screening stage of DHL-PPI, the string matching problem of comparing a protein sequence against a database with M proteins can be transformed into a much more simpler problem: to find a number inside a sorted array of length M. This pre-screening process narrows down the search to a much smaller set of candidate proteins for further confirmation. As a final step, DHL-PPI uses the Hamming distance to verify the final PPI relationship. Conclusions The experimental results confirmed that DHL-PPI is feasible and effective. Using a dataset with strictly negative PPI examples of four species, DHL-PPI is shown to be superior or competitive when compared to the other state-of-the-art methods in terms of precision, recall or F1 score. Furthermore, in the prediction stage, the proposed DHL-PPI reduced the time complexity from $$O(M^2)$$ O ( M 2 ) to $$O(M\log M)$$ O ( M log M ) for performing an all-against-all PPI prediction for a database with M proteins. With the proposed approach, a protein database can be preprocessed and stored for later search using the proposed encoding scheme. This can provide a more efficient way to cope with the rapidly increasing volume of protein datasets.

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the “Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”. However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B (Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induced peroxidative stress damage, and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease's progression. However, Sal B is poorly absorbed orally, and patient compliance is poor when administered intravenously. Therefore, there is an urgent need to find a new non-injection route of drug delivery. In this study, Sal B was used as model drug and l-leucine (LL) as excipient to prepare Sal B dry powder inhaler (Sal B-DPI) by spray drying method. Modern preparation evaluation methods were used to assess the quality of Sal B-DPI. Sal B-DPI is promising for the treatment of IPF, according to studies on pulmonary irritation evaluation, in vivo and in vitro pharmacodynamics, metabolomics, pharmacokinetics, and lung tissue distribution.

Heavy metal pollution in the surface sediments of urban rivers has a significant influence on the safety of city residents. This study explores the features of heavy metal pollution in the surface sediments of the Shuimo River and provides a theoretical basis for decision makers regarding river management and restoration. This study uses principal component analysis and kriging interpolation to analyse the pH values and pollution characteristics of nine heavy metals (As, Pb, Zn, Cu, Ni, Fe, Mn, Cr, and V) in 23 surface sediments of the Shuimo River. The results showed that the pH value of the surface sediments along the direction of water flow had a quadratic curve trend. Kriging interpolation revealed consistency in the spatial distribution of heavy metals and Fe, and the peak value was from Qidaowan to Weihuliang. There were significant positive correlations (p < 0.05) between Fe and Pb; Mn, Cr, V, Cu, and Zn; and Mn, Cr, and V. The principal component analysis showed that the main heavy metals in the surface sediments of the Shuimo River were Fe, Zn, Cu, and As. The total amount of heavy metals was in the order of Fe > Mn > Zn > V > Cr > Ni > Cu > Pb > As, ranging from 11.27~18,760.97 mg·kg−1. The cluster analysis classified the nine heavy metals into four categories: Zn and Cu in the first category; Ni in the second; As and Pb in the third; and V, Cr, Mn, and Fe in the fourth.

Abstract As a variant of highly efficient electrical discharge machining (EDM), the die-sinking mixed-gas atomization discharge ablation process (DMA-DAP) uses an atomized dielectric formed by a mixed gas, which mainly composed of oxygen and supplemented by nitrogen, and water medium as the discharge medium. In this technology, the oxygen in the medium is used for exothermic oxidation, and the vaporization and explosion of the water generates a chip removal force for highly efficient erosion. The present work uses single-factor tests to compare the characteristics of processing the difficult-to-machine material titanium-alloy special-shaped cavities using either DMA-DAP or EDM. The current, pulse width, pulse interval, and dielectric pressure are selected as the single-factor processing parameters, and how they influence the material removal rate (MRR), electrode relative wear rate (ERWR) and the surface morphology of the processed square cavities is analyzed. The results show that with DMA-DAP, the MRR is more than 12 times that of EDM, the ERWR is reduced by more than 98%, and the surface morphology is relatively good. Finally, taking an aero-engine radial diffuser as the profiling object, DMA-DAP realizes a profiling sample in the form of a variable-cross-section cavity that EDM cannot process, and the efficient die-sinking processing ability of DMA-DAP is verified.

Abstract Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

Urbanization not only profoundly alters landscape profiles, ecosystems and vertebrate faunal diversity but also disturbs microbial communities by increasing stochasticity, vulnerability, biotic homogenization, etc. However, because of the buffering effect of host species, microbial communities are expected to be influenced by both host species and urbanization stresses. Therefore, the impacts of urbanization on animals’ microbial symbionts could be more complex and uncertain. In this study, we quantified the urbanization degree of sampling sites and surveyed the gut and skin microbes of three amphibian host species in different sites in urban parks and nearby villages of Chengdu, Southwest China. Furthermore, a co-occurrence network analysis, the phylogenetic normalized stochasticity ratio and Sloan neutral community models were applied to infer the impact of urbanization on symbiotic microbial communities. For the three host species, urbanization increased the diversity of symbiotic microbes and the number of keystone microbial taxa. However, the negative effects of such increased diversification were evident, as the community stochasticity and co-occurrence network structure vulnerability also increased, while the network structure complexity and stability were reduced. Finally, the community stochasticity had positive associations with the network vulnerability, implying that the existence of many transient symbiotic rare microbial taxa in urban parks makes the symbiotic microbial community structure more fragile. Conclusively, urbanization increased the symbiotic microbial diversity at the cost of community stability; the results provide a new perspective for better understanding the complex triangulated environment–host–microbe relationship.

BackgroundAt present, immunotherapy is a very promising treatment method for lung cancer patients, while the factors affecting response are still controversial. It is crucial to predict the efficacy of lung squamous carcinoma patients who received immunotherapy.MethodsIn our retrospective study, we enrolled lung squamous carcinoma patients who received immunotherapy at Beijing Chest Hospital from January 2017 to November 2021. All patients were grouped into two cohorts randomly, the training cohort (80% of the total) and the test cohort (20% of the total). The training cohort was used to build neural network models to assess the efficacy and outcome of immunotherapy in lung squamous carcinoma based on clinical information. The main outcome was the disease control rate (DCR), and then the secondary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsA total of 289 patients were included in this study. The DCR model had area under the receiver operating characteristic curve (AUC) value of 0.9526 (95%CI, 0.9088–0.9879) in internal validation and 0.9491 (95%CI, 0.8704–1.0000) in external validation. The ORR model had AUC of 0.8030 (95%CI, 0.7437–0.8545) in internal validation and 0.7040 (95%CI, 0.5457–0.8379) in external validation. The PFS model had AUC of 0.8531 (95%CI, 0.8024–0.8975) in internal validation and 0.7602 (95%CI, 0.6236–0.8733) in external validation. The OS model had AUC of 0.8006 (95%CI, 0.7995–0.8017) in internal validation and 0.7382 (95%CI, 0.7366–0.7398) in external validation.ConclusionsThe neural network models show benefits in the efficacy evaluation of immunotherapy to lung squamous carcinoma patients, especially the DCR and ORR models. In our retrospective study, we found that neoadjuvant and adjuvant immunotherapy may bring greater efficacy benefits to patients.

Abstract Background Macrophages are the only inflammatory cells that can penetrate the closed nucleus pulposus and their polarization plays an important role in intervertebral disc degeneration (IVDD). This paper attempted to investigate the pathogenesis of IVDD by altering the polarization state of macrophages. Methods Macrophage RAW264.7 cells were induced by interferonγ (IFN‐γ) and lipopolysaccharide (LPS). The polarization of RAW264.7 cells was estimated by western blot and immunofluorescence. The expressions of inflammatory factors were detected by ELISA. Subsequently, RAW264.7 cells were treated with different concentrations of minocycline (Mino) and sinomenine (Sino), followed by the assessment of cell viability with cell counting kit‐8 kit. Then, RAW264.7 cell culture medium was collected for the culture of human nucleus pulposus cells (NPCs). Toluidine blue staining and type II collagen staining were applied to assay the level of type II collagen. The cell apoptosis, oxidative stress, and nitric oxide (NO) level were appraised by TUNEL, oxidative stress kits and NO kit, respectively. Western blot was employed to test the levels of apoptosis‐ and oxidative stress‐related proteins. Results IFN‐γ and LPS could induce M1 polarization of RAW264.7 cells. Mino and Sino could reduce the polarization of RAW264.7 cells toward M1. M1‐polarized medium inhibited LPS‐induced activity, inflammation, and damage of NPCs, which were enhanced by Mino and Sino in medium. Conclusion M1 polarization of macrophages promoted LPS‐induced inflammation and damage of NPCs.

This paper introduces a compact magnetic state-selection cesium atomic clock called LIP Cs-3000 and analyses its characteristics. The test results reveal that the ranges of the line width, peak-to-valley ratio and signal-to-noise ratio of Ramsey pattern are 340–410 Hz, 2–13 and 2,000–8,000 respectively. The corresponding distributions of these parameters are derived by using statistical methods. According to these results, some suggestions are put forward for the further development of the clock. It is also pointed out that the most important factor affecting the accuracy of LIP Cs-3000 atomic clock is the uncertainty of cavity phase shift. In addition, the method to estimate the lifetime of a clock has been proposed. In the end, the paper gives some environmental adaptability designs of the clock, which enable the clock to be used in complex environments.

The diagnosis of bearing faults is an important guarantee for the healthy operation of mechanical equipment. Due to the time-varying working conditions of mechanical equipment, it is necessary to achieve bearing fault diagnosis under time-varying working conditions. However, the superposition of the two-dimensional working conditions of speed and acceleration brings great difficulties to diagnosis via data-driven models. The long short-term memory (LSTM) model based on the infinitesimal method is an effective method to solve this problem, but its performance still has certain limitations. On this basis, this article proposes a model for fault diagnosis under time-varying operating conditions that combines a residual network model (ResNet) and a gate recurrent unit (model) (GRU). Firstly, the samples were segmented, and feature extraction was performed using ResNet. We then used GRU to process the information. Finally, the classification results were output through the output network. This model could ignore the influence of acceleration and achieve high fault diagnosis accuracy under time-varying working conditions. In addition, we used t-SNE to reduce the dimensionality of the features and analyzed the role of each layer in the model. Experiments showed that this method had a better performance compared with existing bearing fault diagnosis methods.

Pampus chinensis is a commercially important fishery species in the Indo-West Pacific region. In the present study, the genetic variation of P. chinensis among 10 sampling localities along the China coast and one from the Indonesia region was evaluated using mitochondrial DNA control region sequences. As a result, a total of 30 variable sites were detected in the 458 bp segment of the control region among 330 individuals from 11 localities, and 41 haplotypes were defined. Samples in the China coast present a high level of genetic diversity, with the values of haplotype diversity ranged from 0.674 to 0.860, and nucleotide diversity from 0.820% to 1.502%. Pairwise FST statistics showed a moderate genetic divergence (−0.027 to 0.384) among samples from different geographical locations. Median-joining network analysis revealed a similar pattern of phylogeographic structure in samples from Ningbo and Dongxing although they were far apart. Therefore, joint influences of dispersal capability, spatial distance, ocean current and geographic segregation on the formation of the present population structure in P. chinensis was proposed. The results of the present study would be helpful for the sustainable utilization and management of this species.

Abstract Although nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood–brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood–brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

The master manipulator is an important part for minimally invasive surgical （MIS）robot. It is used to receive the doctor action and control the slave operator to complete the surgical operation. Based on analysis of the application requirements of the master manipulator that is already existed，the configuration design requirements of the master manipulator are analyzed，and the configuration design of the master manipulator is completed. The trajectory planning simulation of the master manipulator in joint space is also carried out，and the displacement，velocity and acceleration curves of the master manipulator joint are obtained. The simulation results show that，the configuration design of the master manipulator is reasonable，and the master manipulator moves smoothly，which lays a theoretical foundation of the further design and optimization for the master manipulator.

Background and objective Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC. Methods Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles. Results Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity. Conclusion Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.

Based on the principles of mass conservation, chemical equilibrium, and electron charge neutrality, a thermodynamic equilibrium system was established for the nickel-cobalt-manganese sulfate leaching solution in the recovery process of spent lithium-ion batteries. By changing the ion concentration in the system, calculating the pH value, and identifying the complexes of Cu2+, Fe3+, PO43−, Al3+, and F− in the system, the results were obtained and used to draw the thermodynamic diagram. The solution thermodynamic calculation and experiment were combined to purify the nickel-cobalt-manganese-rich leachate. The results show that the main Cu2+, Fe3+, PO43−, Al3+, and F− impurity ions could all be reduced to less than 10 ppm under the optimized process parameters.

The occurrence of bisphenol A (BPA) and its structural analogs, known as endocrine disruptors is widely reported. Consumers could be exposed to these chemicals through canned foods, leading to health risks. Considerable advances have occurred in the pathogenic mechanism, migration law, and analytical methodologies for these compounds in canned foods. However, the confusion and controversies on sources, migration, and health impacts have plagued researchers. This review aimed to provide insights and perspectives on sources, migration, effects on human health, and surveillance of these chemicals in canned food products. Current trends in the determination of BPA and its structural analogs have focused on mass spectroscopy and electrochemical sensor techniques. Several factors, including pH, time, temperature, and volume of the headspace in canned foods, could affect the migration of the chemicals. Moreover, it is necessary to quantify the proportion of them originating from the can material used in canned product manufacturing. In addition, adverse reaction research about exposure to low doses and combined exposure with other food contaminants will be required. We strongly believe that the information presented in this paper will assist in highlighting the research needs on these chemicals in canned foods for future risk evaluations.

Abstract This study aims to develop an artificial intelligence (AI)-based model to assist radiologists in pneumoconiosis screening and staging using chest radiographs. The model, based on chest radiographs, was developed using a training cohort and validated using an independent test cohort. Every image in the training and test datasets were labeled by experienced radiologists in a double-blinded fashion. The computational model started by segmenting the lung field into six subregions. Then, convolutional neural network classification model was used to predict the opacity level for each subregion respectively. Finally, the diagnosis for each subject (normal, stage I, II, or III pneumoconiosis) was determined by summarizing the subregion-based prediction results. For the independent test cohort, pneumoconiosis screening accuracy was 0.973, with both sensitivity and specificity greater than 0.97. The accuracy for pneumoconiosis staging was 0.927, better than that achieved by two groups of radiologists (0.87 and 0.84, respectively). This study develops a deep learning-based model for screening and staging of pneumoconiosis using man-annotated chest radiographs. The model outperformed two groups of radiologists in the accuracy of pneumoconiosis staging. This pioneer work demonstrates the feasibility and efficiency of AI-assisted radiography screening and diagnosis in occupational lung diseases.

Considering the importance of start-up characteristics of the rubidium atomic clock in engineering applications, the objective of this paper is to optimize the start-up characteristics of the rubidium atomic clock by studying the theory of the rubidium atomic frequency standards, especially the light pumping process, and the effect of light intensity on frequency accuracy. Our analysis demonstrated that frequency accuracy is proportional to the light intensity, and hence, we propose a method for actively optimizing the start-up characteristics of the rubidium atomic clock by utilizing the fluctuations in light intensity. Additionally, some related experiments using the proposed method indicate that the light intensity–frequency coefficient of the rubidium atomic clock is improved from 1.84 × 10−9 to 4.21 × 10−10 V−1 within 30 min after the rubidium atomic clock is locked, and also, the lockout time is less than 5 min with a wide working temperature range (0–50 °C), indicating a significant improvement in the start-up characteristics of the rubidium atomic clock.

BackgroundTelemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. ObjectiveThis systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. MethodsWe systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. ResultsA total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference −0.71, 95% CI −1.07 to −0.36; P

Depressive disorders are a severe psychiatric and social problem that affect more than 4% of the global population. Depressive disorders have explicit hereditary characteristics; however, the precise driving genetic force behind these disorders has not yet been clearly illustrated. In the present study, we recruited a three-generation Chinese pedigree in which 5 of 17 members had long-term depression. We conducted whole-exome sequencing to identify the genetic mutation profiles of the family, and a list of susceptible genetic variations that were highly associated with depression onset was revealed via multiple omics analysis. In particular, a non-synonymous single nucleotide variation in the oxoglutarate dehydrogenase-like (OGDHL) gene, rs2293239 (p.Asn725Ser), was identified as one of the major driving genetic forces for depression onset in the family. This variant causes an important conformational change in the transketolase domain of OGDHL, thus reducing its binding affinity with the cofactor thiamine pyrophosphate and eventually resulting in the abnormal accumulation of glutamate in the brain. Brain imaging analysis further linked the rs2293239 variant with an enlarged amygdala and cerebellum in depressive family members. In summary, the present study enhances the current genetic understanding of depressive disorders. It also provides new options for prioritizing better clinical therapeutic regimens, as well as identifying a new protein target for the design of highly specific drugs to treat depressive disorders.

Abstract Background Poor targeting and penetration of chemotherapy drugs in solid tumors, and the development of resistance to chemotherapeutic agents are currently hindering the therapy of breast cancer; meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy. Results A multi-functional nano-platform containing gambogic acid (GA) and paclitaxel (PTX) was characterized by a small size, high encapsulation efficiency, slow release, long systemic circulation time in vivo, showed good targeting and penetrability to tumor tissues and tumor cells, and exhibited higher anti-tumor effect and lower systemic toxicity in BALB/c mice bearing 4T1 tumor. GA not only overcame the multidrug resistance of PTX by inhibiting P-glycoprotein (P-gp) activity in MCF-7/ADR cells, but also inhibited MDA-MB-231 cells migration and invasion, playing a crucial role in preventing and treating the lung metastasis of breast cancer caused by PTX; meanwhile, the synergistic anti-tumor effect of GA and PTX has also been verified in vitro and in vivo experiments. Conclusion Our data described the better recognition and penetration of tumor cells of R9dGR-modified versatile nanosystems containing GA and PTX, which exerted one stone three birds clinical therapeutic efficacy of multifunctionality.

Here, the authors characterize replication of SARS-CoV-2 in human airway epithelial (HAE) cultures and show that it can infect ciliated and secretory cells, affects transepithelial electrical resistance and causes plaque-like cytopathic effects associated with apoptosis.