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Abstract To explore the performance of 99mTc-diethylene triaminepentaacetic acid (DTPA) SPECT/CT texture analysis in evaluating the activity of thyroid-associated ophthalmopathy (TAO) . This retrospective study examined 115 TAO patients from a single institution as an internal cohort and 58 TAO patients from another institution as an external validation set. Patients in the internal cohort were randomly divided into training (n = 81) and internal validation sets (n = 34). Radiomics signatures were constructed with the minimal redundancy maximal relevance and least absolute shrinkage and selection operator algorithms in training set. Multivariate logistic regression analysis was used to develop a clinical model and a combined clinical–radiomics model. Diagnostic performance of models was evaluated using receiver operating characteristic curve analysis, calibration curves and decision curve analysis. Compared with CT and SPECT radiomics models, Rad-scoreSPECT/CT demonstrated the best performance with areas under the receiver operating characteristic curve of 0.94 and 0.91 in the training and test sets, respectively. The combined clinical-radiomics model exhibited significantly better performance in evaluating TAO activity. Our results demonstrate the validity of a multimodal radiomic model of 99mTc-DTPA-SPECT/CT to assess TAO activity. The combined clinical-radiomics model exhibited significantly better diagnostic performance than the clinical model.

Abstract Introduction Non-alcoholic fatty liver disease (NAFLD) and obesity have become one of the most common chronic diseases, and the global prevalence is increasing year by year. Both are accompanied by hypersensitive C-reactive protein (hs-CRP). At present, there are many predictors of NAFLD. Exploring the relationship between hs-CRP and nonalcoholic fatty liver disease in non-obese people will be helpful for risk prediction and clinical screening in high-risk populations. Objective To explore the relationship between levels of serum hs-CRP and the presence of NAFLD in non-obese people. Methods A total of 6558 participants who underwent physical examination from March 2017 to November 2017. Multivariate logistic regression was utilized to analyze the risk factors associated with NAFLD. Results This study including 4240 males and 2318 females ranging from 20 to 94 years. In 1396 patients with NAFLD, the prevalence rate was 21.3%, among which 1056 (24.9%) males and 340 (14.7%) females had NAFLD. The prevalence of NAFLD was much higher in males compared to females (χ 2 = 93.748, P

Abstract Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Abstract Background Mastery may shape the way individuals cope with life challenges and influence cognitive function in later life. Mastery grows out of traumatic experience and could change over the life course. This study examined the within-person and between-person associations of mastery and cognitive function, and if these associations were moderated by age in the United States. Method Data were derived from three time points (2006–2008, 2010–2012, and 2014–2016) of the Health and Retirement Study, with 14,461 adults (aged 51 or above). Cognitive function was measured through a 27-point Telephone Interview Cognitive Screen (TICS). Mastery was measured by a modified Pearlin Mastery Scale. Multilevel modeling was employed to analyze the data. Results Both within-person ( $$\beta$$ β =0.124, SE = 0.023, p

Abstract DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures. Graphical Abstract Spherical DNA framework showed predominant liver retention to rescue hepatic 870 ischemia reperfusion injury

ABSTRACT: This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low.

1,4-butanediol (1,4-BDO) is an important building block in the chemical industry that has been mainly produced from fossil fuels, but now biosynthesis of 1,4-BDO has received more and more attention due to environmental issues. The Clostridia C4 pathway produces an intermediate crotonyl-CoA which could be diverted to 1,4-BDO by 4-hydroxybutyryl-CoA dehydratase (4HBD). Here, we compared this pathway with other 1,4-BDO biosynthesis pathways and illustrated its potential advantages regarding cellular energy conservation and theoretical yield. Then, the feasibility of 1,4-BDO production in this way was tested by introducing a single 4HBD in Clostridium acetobutylicum that natively produced the C4 intermediate and a variety of aldehyde/alcohol dehydrogenases (AdhE). Five different 4HBD genes were screened and the Cbei-2100 gene from Clostridium beijerinckii was the most effective, producing 0.066 mg/mL of 1,4-BDO. To block the metabolic flux towards the main product butanol, disruption of butyryl-CoA dehydrogenase (Bcd) was tried but failed, while inactivation of its homologue (FAD/FMN-containing dehydrogenase, Fcd) obtained little effect. Alternatively, the electron-transferring flavoprotein EtfA coupled with Bcd was inactivated, and 1,4-BDO production was greatly increased to 0.182 mg/mL. In conclusion, this study demonstrated the feasibility of 1,4-BDO production through the Clostridia C4 pathway. Further blocking of the competing flux towards butanol would be effective to improve the production of in the future.

Abstract Chloroplasts play a vital role in plant growth and development, which are the main sites of photosynthesis and the production of hormones and metabolites. Despite their significance, the regulatory mechanisms governing chloroplast development remain unclear. In our investigation, we identified a rice mutant with defective chloroplasts in rice (Oryza sativa L.), named albino lethal 13 (osal13), which displayed a distinct albino phenotype in leaves, ultimately resulting in seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel rice protein with no homologous gene or known conserved domain. This gene was located in the chloroplast and exhibited constitutive expression in various tissues, particularly in green tissues and regions of active cell growth. Our study's findings reveal that RNAi‐mediated knockdown of OsAL13 led to a pronounced albino phenotype, reduced chlorophyll and carotenoid contents, a vesicle chloroplast structure, and a decrease in the expression of chloroplast‐associated genes. Consequently, the pollen fertility and seed setting rate were lower compared with the wild type. In contrast, the overexpression of OsAL13 resulted in an increased photosynthetic rate, a higher total grain number per panicle, and enhanced levels of indole‐3‐acetic acid (IAA) in the roots and gibberellin A3 (GA3) in the shoot. These outcomes provide new insights on the role of OsAL13 in regulating chloroplast development in rice.

BackgroundPrevious neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients.MethodsA comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software.Results13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients.ConclusionThis meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

Abstract To enhance the ribonucleic acid (RNA) productivity for industrial applications, this study employed strain screening and medium optimization to improve the content of RNA in Cyberlindnera jadinii. A rapid screening method, combining atmospheric and room temperature plasma mutagenesis, 48-deep-well plates fermentation, and microplate reader detection, was developed. A mutant strain named WB15 with high RNA content was successfully obtained, exhibiting the RNA content of 156 ± 4.5 mg/g DCW, 1.4 times of the starting strain CCTCC AY 92020. Furthermore, Plackett–Burman design and response surface methodology were employed to identify three significant factors (yeast extract, soybean peptone, and KH2PO4) affecting the RNA content. By utilizing the optimal medium composed of 13.43 g/L yeast extract, 12.12 g/L soybean peptone and 2.78 g/L KH2PO4, the RNA content of WB15 further increased to 184 ± 4.9 mg/g DCW. Additionally, the mutant strain WB15 exhibited a greater cellular width compared to AY 92020, along with increased growth rate and single-cell RNA content by 22% and 48.9%, respectively. Perturbations in ribosome assembly, specifically a reduction in the ratio of ribosomal proteins to ribosomal RNA of the large subunit, might indirectly contribute to the higher RNA content in the WB15 strain. Overall, the combination of rapid screening with fermentation medium optimization proved to be an effective approach for improving the RNA content of C. jadinii, thus facilitating the industrial production of RNA.

Regional integrated energy system (RIES) cluster, i.e., multi-source integration and multi-region coordination, is an effective approach for increasing energy utilization efficiency. The hierarchical architecture and limited information sharing of RIES cluster make it difficult for traditional game theory to accurately describe their game behavior. Thus, a hierarchical game approach considering bounded rationality is proposed in this paper to balance the interests of optimizing RIES cluster under privacy protection. A Stackelberg game with the cluster operator (CO) as the leader and multiple RIES as followers is developed to simultaneously optimize leader benefit and RIES utilization efficiency. Concurrently, a slight altruistic function is introduced to simulate the game behavior of each RIES agent on whether to cooperate or not. By introducing an evolutionary game based on bounded rationality in the lower layer, the flaw of the assumption that participants are completely rational can be avoided. Specially, for autonomous optimal dispatching, each RIES is treated as a prosumer, flexibly switching its market participation role to achieve cluster coordination optimization. Case studies on a RIES cluster verify effectiveness of the proposed approach.

Introduction: It is known that patients with immune-abnormal co-pregnancies are at a higher risk of adverse pregnancy outcomes. Traditional pregnancy risk management systems have poor prediction abilities for adverse pregnancy outcomes in such patients, with many limitations in clinical application. In this study, we will use machine learning to screen high-risk factors for miscarriage and develop a miscarriage risk prediction model for patients with immune-abnormal pregnancies. This model aims to provide an adjunctive tool for the clinical identification of patients at high risk of miscarriage and to allow for active intervention to reduce adverse pregnancy outcomes.Methods: Patients with immune-abnormal pregnancies attending Sichuan Provincial People’s Hospital were collected through electronic medical records (EMR). The data were divided into a training set and a test set in an 8:2 ratio. Comparisons were made to evaluate the performance of traditional pregnancy risk assessment tools for clinical applications. This analysis involved assessing the cost-benefit of clinical treatment, evaluating the model's performance, and determining its economic value. Data sampling methods, feature screening, and machine learning algorithms were utilized to develop predictive models. These models were internally validated using 10-fold cross-validation for the training set and externally validated using bootstrapping for the test set. Model performance was assessed by the area under the characteristic curve (AUC). Based on the best parameters, a predictive model for miscarriage risk was developed, and the SHapley additive expansion (SHAP) method was used to assess the best model feature contribution.Results: A total of 565 patients were included in this study on machine learning-based models for predicting the risk of miscarriage in patients with immune-abnormal pregnancies. Twenty-eight risk warning models were developed, and the predictive model constructed using XGBoost demonstrated the best performance with an AUC of 0.9209. The SHAP analysis of the best model highlighted the total number of medications, as well as the use of aspirin and low molecular weight heparin, as significant influencing factors. The implementation of the pregnancy risk scoring rules resulted in accuracy, precision, and F1 scores of 0.3009, 0.1663, and 0.2852, respectively. The economic evaluation showed a saving of ¥7,485,865.7 due to the model.Conclusion: The predictive model developed in this study performed well in estimating the risk of miscarriage in patients with immune-abnormal pregnancies. The findings of the model interpretation identified the total number of medications and the use of other medications during pregnancy as key factors in the early warning model for miscarriage risk. This provides an important basis for early risk assessment and intervention in immune-abnormal pregnancies. The predictive model developed in this study demonstrated better risk prediction performance than the Pregnancy Risk Management System (PRMS) and also demonstrated economic value. Therefore, miscarriage risk prediction in patients with immune-abnormal pregnancies may be the most cost-effective management method.

BackgroundNo consistent conclusion has been reached regarding the attentional bias characteristics of adolescents with major depressive disorders (MDD), and unexamined co-occurring anxiety distress may contribute to this inconsistency.MethodsWe enrolled 50 MDD adolescents with anxiety distress, 47 MDD adolescents without anxiety distress and 48 healthy adolescents. We measured attentional bias using a point-probe paradigm during a negative-neutral emotional face task. Reaction time, correct response rate and attentional bias value were measured.ResultsMDD adolescents did not show a negative attentional bias; MDD adolescents with anxiety distress exhibited longer reaction time for negative and neutral stimuli, lower correct response rate for negative stimuli. Hamilton Anxiety Scale scores were positively correlated with reaction time, negatively correlated with correct response rate, and not significantly correlated with attentional bias value.LimitationsThe cross-sectional design hinders causal attribution, and positive emotional faces were not included in our paradigm.ConclusionNegative attentional bias is not a stable cognitive trait in adolescents with MDD, and avoidance or difficulty in disengaging attention from negative emotional stimuli may be the attentional bias characteristic of MDD adolescents with anxiety distress.

Abstract Since the total number of the antenna elements can be up to hundreds in a massive multiple‐input multiple‐output (MIMO) system, subarray‐structured base station (BS) array configurations are widely adopted to achieve a good cell coverage and to reduce the required number of radio frequency chains at the same time. It is crucial for any BS product to ensure that the antenna elements perform correctly as expected. Therefore, the necessity of array diagnosis is evident, especially for large BS arrays. Furthermore, it is essential that the diagnosis can be achieved in a compact and cost‐effective setup with high measurement efficiency (i.e. only a few measurement samples are required). The principle of the diagnosis method presented in this article is to obtain the S‐parameters between the subarrays and the probe via solving linear equations. In the simulation, a BS array composed of 16 subarrays with each containing 3 elements is used to validate the diagnosis method at 3.5 GHz. An array composed of 4 subarrays with each containing 3 elements was used in the measurements to verify the diagnosis method with two different phase tuning matrices at 3 GHz. Successful diagnosis results have been achieved in both the simulations and the measurements.

Cuttlefish bones are byproducts of cuttlefish processing and are readily available in the marine food industry. In this study, calcium phosphate bioceramics were prepared from cuttlefish bones using a two-stage hydrothermal calcination process. The results indicated that all bioceramics derived from cuttlefish bones had a higher degradation capacity, better bone-like apatite formation ability, and higher degree of osteogenic differentiation than commercially available hydroxyapatite. Notably, β-tricalcium phosphate, which had the highest degree of Ca2+ and Sr2+ dissolution among the bioceramics extracted, can significantly upregulate osteogenic markers (alkaline phosphatase, osteocalcin) and stimulate bone matrix mineralization. Thus, it is a promising bioceramic material for applications in bone regeneration.

Abstract The Dahua Lou loom, pivotal to Nanjing Yunjin weaving, constitutes an integral part of global intangible cultural heritage. Its intricate weaving technique remains unmatched by modern machinery, marking it as a vital cultural artefact warranting protection. However, current virtual interactive systems grapple with adequately demonstrating its craftsmanship due to limitations like system iteration, multi-system integration, and data interoperability. To address these challenges, this study proposes a method that synergizes knowledge ontology, virtual reality technology, and data-driven design.Knowledge ontology enables enhanced management, reuse, and wide-ranging dissemination of domain knowledge, improving system interoperability. This methodology is utilized in constructing the loom model, animation demonstration, and in integrating it into the virtual interactive system. This multifaceted application of knowledge ontology significantly bolsters the system’s efficiency and optimizes its development, maintenance, and integration processes.This research provides crucial advancements in domain knowledge modeling, 3D visualization, and virtual reality interactive systems, playing a significant role in preserving cultural heritage. Despite certain limitations, it offers an immersive, intuitive, and enriched design experience. The study concludes with a critique of the developed system, discussions on the encountered challenges, and future research directions include improving and expanding the knowledge ontology based on the opinions and practical experiences of domain experts, enhancing system compatibility, and conducting broader evaluations.

Characterized by severe deficits in communication, most individuals with autism spectrum conditions (ASC) experience significant language dysfunctions, thereby impacting their overall quality of life. Wernicke's area, a classical and traditional brain region associated with language processing, plays a substantial role in the manifestation of language impairments. The current study carried out a mega-analysis to attain a comprehensive understanding of the neural mechanisms underpinning ASC, particularly in the context of language processing. The study employed the Autism Brain Image Data Exchange (ABIDE) dataset, which encompasses data from 443 typically developing (TD) individuals and 362 individuals with ASC. The objective was to detect abnormal functional connectivity (FC) between Wernicke's area and other language-related functional regions, and identify frequency-specific altered FC using Wernicke's area as the seed region in ASC. The findings revealed that increased FC in individuals with ASC has frequency-specific characteristics. Further, in the conventional frequency band (0.01–0.08 Hz), individuals with ASC exhibited increased FC between Wernicke's area and the right thalamus compared with TD individuals. In the slow-5 frequency band (0.01–0.027 Hz), increased FC values were observed in the left cerebellum Crus II and the right lenticular nucleus, pallidum. These results provide novel insights into the potential neural mechanisms underlying communication deficits in ASC from the perspective of language impairments.

The mental well-being of PhD students is a major concern in higher education. However, very few studies have investigated the influencing factors of PhD students’ subjective well-being (SWB) – an important indicator of mental well-being. Even no study on the influencing factors of PhD students’ SWB has been undertaken in mainland China. Based on job demands–resources theory, the present study pioneers the investigation of the relationship between PhD students’ psychological capital (PsyCap; comprising self-efficacy, hope, resilience, and optimism) and SWB (comprising positive affect, negative affect, and life satisfaction) in mainland China. It further examined the mediating role of academic engagement (comprising vigor, dedication, and absorption) in this relationship. PhD students (n = 376) from two comprehensive universities in Jiangsu province responded to an online survey. The results showed that (1) self-efficacy was positively associated with life satisfaction, hope was positively associated with positive affect, optimism was significantly associated with all three dimensions of SWB, but resilience was not significantly associated with any of the three SWB dimensions; and (2) dedication mediated the relationship between hope and life satisfaction and that between optimism and negative affect and life satisfaction, but vigor and absorption did not mediate any of the PsyCap–SWB relationships. Limitations and practical implications of this study are discussed.

AbstractBackground Non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) are both associated with obesity. However, the relationship of NAFLD with reflux esophagitis (RE) is still unclear in non-obese individuals.Methods Individuals with a body mass index (BMI) of 28 kg/m2 or higher, as well as waist circumference (WC) no less than 90 cm for men and no less than 85 cm for women were excluded. After controlling for other factors, 1905 eligible adult subjects were included. The components related to metabolic syndrome and the prevalence of NAFLD in the RE group as well as the non-RE group were analyzed. Risk factors for RE were determined using logistic regression.Results In non-obese individuals, the prevalence of RE and NAFLD increased with increasing WC and BMI (p

Abstract Background Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose–response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations. Methods We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose–response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. Results Forty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose–response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer. Conclusions An increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain. Trial registration PROSPERO: CRD42020152223

Human epidermal growth factor (hEGF) holds significant importance in the fields of medicine and cosmetics. Therefore, it becomes imperative to develop a highly efficient fermentation system for hEGF production. In this study, a stable hEGF-secreting expression strain was created by integrating the hEGF gene into the genome of Escherichia coli (E. coli) BL21, and an immobilized fermentation system was developed based on biofilm to facilitate continuous hEGF production. After optimization of fermentation conditions and gene dosage, the production of hEGF was increased from 13.9 mg/L to 52.4 mg/L in free-cell fermentation. Moreover, genetic modifications targeting dgcC, csgD, bcsA, and bcsB proved to enhance biofilm formation. When the bcsB was overexpressed in BL21-hEGF-C5, the biofilm-forming ability was enhanced by 91.1% and the production of hEGF was increased by 28% in biofilm-immobilized continuous fermentation. In conclusion, this study successfully confirms the feasibility of continuous hEGF production through the biofilm system of E. coli, providing valuable insights for the development of other proteins in the field of continuous biomanufacturing.

Thousands of lncRNAs have been found in zebrafish embryogenesis and adult tissues, but their identification and organogenesis-related functions have not yet been elucidated. In this study, high-throughput sequencing was performed at three different organogenesis stages of zebrafish embryos that are important for zebrafish muscle development. The three stages were 10 hpf (hours post fertilization) (T1), 24 hpf (T2), and 36 hpf (T3). LncRNA gas5, associated with muscle development, was screened out as the next research target by high-throughput sequencing and qPCR validation. The spatiotemporal expression of lncRNA gas5 in zebrafish embryonic muscle development was studied through qPCR and in situ hybridization, and functional analysis was conducted using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9, CRISPR/Cas9). The results were as follows: (1) A total of 1486 differentially expressed lncRNAs were identified between T2 and T1, among which 843 lncRNAs were upregulated and 643 were downregulated. The comparison with T3 and T2 resulted in 844 differentially expressed lncRNAs, among which 482 lncRNAs were upregulated and 362 lncRNAs were downregulated. A total of 2137 differentially expressed lncRNAs were found between T3 and T1, among which 1148 lncRNAs were upregulated and 989 lncRNAs were downregulated, including lncRNA gas5, which was selected as the target gene. (2) The results of spatiotemporal expression analysis showed that lncRNA gas5 was expressed in almost all detected embryos of different developmental stages (0, 2, 6, 10, 16, 24, 36, 48, 72, 96 hpf) and detected tissues of adult zebrafish. (3) After lncRNA gas5 knockout using CRISPR/Cas9 technology, the expression levels of detected genes related to muscle development and adjacent to lncRNA gas5 were more highly affected in the knockout group compared with the control group, suggesting that lncRNA gas5 may play a role in embryonic muscle development in zebrafish. (4) The results of the expression of the skeletal myogenesis marker myod showed that the expression of myod in myotomes was abnormal, suggesting that skeletal myogenesis was affected after lncRNA gas5 knockout. The results of this study provide an experimental basis for further studies on the role of lncRNA gas5 in the embryonic skeletal muscle development of zebrafish.

As urbanization accelerates, a growing influx of pollutants enters the sea through land runoff, posing a threat to coastal ecosystems. In this study, we systematically determined the concentrations of nutrients and heavy metals in the water and sediments of coastal areas (Yantai, China) and assessed their sources and ecological risks. The results showed that inland rivers transported large amounts of NO3− and PO43− into coast water, which caused severe eutrophication. Regarding heavy metals, copper dominated in seawater, whereas plumbum and arsenic were dominant in sediment, which was sourced from aerosol deposition and mariculture. Zinc, chromium, copper, mercury, and cadmium contributed slightly to pollution, with low enrichment factors, mainly from natural sources. Further analysis showed that zinc, mercury, copper, and arsenic were significantly affected by the grain size composition in sediment. Ecological risk assessment indicated that the coastal zone of Yantai City is in a state of light heavy-metal pollution.

The effect of the external electric field on the electronic structure, magnetic properties, dielectric function and absorption properties of monolayers NiZr are investigated in this manuscript. It is found that monolayer NiZr exhibits antiferromagnetic, ferrimagnetic, and ferromagnetic properties under the external electric field. The magnetic property is affected by both the crystal field and the external electric field, and the magnetic moment is nonlinearly related to the intensity of the external electric field. Under the electric field −0.01 V/Å and 0.055 V/Å, the ferromagnetism of monolayer NiZr is stable, while is unstable under other electric field. The magnetic property mainly comes from the spin of Zr atom, and the electron transfer between Ni atom and Zr atom is not equal, indicating the existence of free electrons and p-d hybrid orbitals. The Ni d orbital and Zr d orbital are split into dxy, dyz, dxz, dxx-yy, and dzz five orbitals. The Zr dzx and Ni dzy orbital spin are primary contributed to the magnetic properties of monolayers NiZr under electric field of −0.01 V/Å; whereas Zr dxx-yy and Ni dxx-yy orbitals spin contribute primarily under 0.055 V/Å. The dielectric constant and absorption characteristics are increased, the anisotropy is weakened, and the effect of electric field on the absorption characteristics is weakened under the [110] direction electric polarization. Therefore, [110] direction electric polarization is beneficial in improving the absorption characteristics of monolayers NiZr.

Summary: The recovery of spent lithium-ion batteries has not only economic value but also ecological benefits. In this paper, molten-salt electrolysis was employed to recover spent LiCoO2 batteries, in which NaCl-Na2CO3 melts were used as the electrolyte, the graphite rod and the mixtures of the spent LiCoO2 cathode and anode were used as the anode and cathode, respectively. During the electrolysis, the LiCoO2 was electrochemically reduced to Co, and Li+ and O2− entered into the molten salt. The O2− was discharged at the anode to generate CO2 and formed Li2CO3. After electrolysis, the cathodic products were separated by magnetic separation to obtain Co and graphite, and Li2CO3 was recovered by water leaching. The recovery efficiencies of Li, Co, and graphite reached 99.3%, 98.1%, and 83.6%, respectively. Overall, this paper provides a simple and efficient electrochemical method for the simultaneous recovery of the cathode and the anode of spent LiCoO2 batteries.

BackgroundIrritable bowel syndrome (IBS) is a brain-gut disorder with high global prevalence, resulting from abnormalities in brain connectivity of the default mode network and aberrant changes in gray matter (GM). However, the findings of previous studies about IBS were divergent. Therefore, we conducted a meta-analysis to identify common functional and structural alterations in IBS patients.MethodsAltogether, we identified 12 studies involving 194 IBS patients and 230 healthy controls (HCs) from six databases using whole-brain resting state functional connectivity (rs-FC) and voxel-based morphometry. Anisotropic effect-size signed differential mapping (AES-SDM) was used to identify abnormal functional and structural changes as well as the overlap brain regions between dysconnectivity and GM alterations.ResultsFindings indicated that, compared with HCs, IBS patients showed abnormal rs-FC in left inferior parietal gyrus, left lingual gyrus, right angular gyrus, right precuneus, right amygdala, right median cingulate cortex, and left hippocampus. Altered GM was detected in the fusiform gyrus, left triangular inferior frontal gyrus (IFG), right superior marginal gyrus, left anterior cingulate gyrus, left rectus, left orbital IFG, right triangular IFG, right putamen, left superior parietal gyrus and right precuneus. Besides, multimodal meta-analysis identified left middle frontal gyrus, left orbital IFG, and right putamen as the overlapped regions.ConclusionOur results confirm that IBS patients have abnormal alterations in rs-FC and GM, and reveal brain regions with both functional and structural alterations. These results may contribute to understanding the underlying pathophysiology of IBS.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022351342.

Abstract In recent years, radiometals have been successfully applied to medicine because of their breadth of decay properties and increased production and availability. Bifunctional chelators play a key role in radiometal‐based radiopharmaceuticals, affecting the labeling, targeting, and pharmacokinetics of bioconjugations and ensuring the stable complexation of the metal in vivo. The capacity of macrocycles to form complexes with extremely high thermodynamics, kinetics, and stability compared to acyclic chelators continues to pique the curiosity of pharmacists and biochemists among all prospective chelators utilized for the radiometal chelation. As new imaging modalities and therapeutic targets develop, the discovery of novel ligand structures with suitable chemical and biological features encourages the modification of chelators with charge and chemical properties. Herein, we present a comprehensive review of developments of macrocyclic chelators for PET radiopharmaceuticals, including innovative chelating agents with new structures and known chelating agent modifications, and their physical‐chemical properties, as well as their biological characteristics and applications in vivo.

Abstract The service life of an artificial hip joint is limited to 10–15 years, which is not ideal for young patients. To extend the lifespan of these prostheses, the coefficient of friction and wear resistance of metallic femoral heads must be improved. In this study, a Cu‐doped titanium nitride (TiNX–Cu) film with “autoantifriction” properties is deposited on a CoCrMo alloy via magnetron sputtering. When delivered in a protein‐containing lubricating medium, the Cu in TiNX–Cu quickly and consistently binds to the protein molecules in the microenvironment, resulting in the formation of a stable protein layer. The proteins adsorbed on the TiNX–Cu surface decompose into hydrocarbon fragments owing to the shear stress between the Al2O3/TiNX–Cu tribopair. The synergistic effect of the catalysis of Cu and shear stress between the Al2O3/TiNX–Cu tribopair transforms these fragments into graphite‐like carbon tribofilms with an antifriction property. These tribofilms can simultaneously reduce the friction coefficient of the Al2O3/TiNX–Cu tribopair and enhance the wear resistance of the TiNX–Cu film. Based on these findings, it is believed that the autoantifriction film can drive the generation of antifriction tribofilms for lubricating and increasing the wear resistance of prosthetic devices, thereby prolonging their lifespan.

In the application of brain-computer interfaces (BCIs), electroencephalogram (EEG) signals are difficult to collect in large quantities due to the non-stationary nature and long calibration time required. Transfer learning (TL), which transfers knowledge learned from existing subjects to new subjects, can be applied to solve this problem. Some existing EEG-based TL algorithms cannot achieve good results because they only extract partial features. To achieve effective transfer, a double-stage transfer learning (DSTL) algorithm which applied transfer learning to both preprocessing stage and feature extraction stage of typical BCIs was proposed. First, Euclidean alignment (EA) was used to align EEG trials from different subjects. Second, aligned EEG trials in the source domain were reweighted by the distance between the covariance matrix of each trial in the source domain and the mean covariance matrix of the target domain. Lastly, after extracting spatial features with common spatial patterns (CSP), transfer component analysis (TCA) was adopted to reduce the differences between different domains further. Experiments on two public datasets in two transfer paradigms (multi-source to single-target (MTS) and single-source to single-target (STS)) verified the effectiveness of the proposed method. The proposed DSTL achieved better classification accuracy on two datasets: 84.64% and 77.16% in MTS, 73.38% and 68.58% in STS, which shows that DSTL performs better than other state-of-the-art methods. The proposed DSTL can reduce the difference between the source domain and the target domain, providing a new method for EEG data classification without training dataset.

Abstract Background Immune cells and stromal cells in the tumor microenvironment play a vital role in the progression of colorectal cancer (CRC). The study aimed to screen valuable prognostic biomarkers in CRC based on stromal and immune scores. Method The ESTIMATE algorithm was used to calculate the immune and stromal scores of CRC samples in TCGA. Then samples were divided into high and low score groups based on the median value of the scores. Differentially expressed genes (DEGs) associated with immune and stromal scores were screened. WGCNA and univariate COX regression analysis were performed to further identify key prognostic genes. Analysis of scRNA-seq for CRC was used for verifying the main source of the key genes. The prognostic value of they was validated based on The Gene Expression Profiling Interactive Analysis and GSE17536 dataset. TIMER and CIBERSORT algorithms were applied to analyze the correlations among key genes and tumor-infiltrating immune cells. Several pairs of colon cancer tissue were used to be proven. Result 1314 upregulated and 4 downregulated genes were identified, which were significantly enriched in immune-related biological processes and pathways. Among these DEGs, SPOCK1 and POSTN were identified as key prognostic genes and mainly expressed in cancer-associated fibroblasts for CRC. High expression of SPCOK1 and POSTN was associated with advanced clinical stage, T stage, N stage, and poor prognosis of CRC. The results from CIBERSORT and TIMER revealed that SPOCK1 and POSTN were associated with tumor-infiltrating immune cells, especially macrophages and neutrophils. Meanwhile, in several pairs of human colorectal tissue samples, SPOK1 and POSTN were found to be significantly overexpressed in colorectal tissue compared with para-cancer tissue, and macrophage surface markers CD68 (co-expressed by M1 and M2 macrophages) and CD206 (M2-specific macrophage expression) were also overexpressed in cancer tissue. Besides, SPOCK1 and POSTN expression were positively correlated with the expression of immune checkpoints. Conclusion Collectively, our results indicate that SPOCK1 and POSTN associated with CAF may be novel prognostic biomarkers in CRC and correlate with immune infiltrates.

Abstract The kidney is a vital organ responsible for maintaining homeostasis in the human body. However, renal cell carcinoma (RCC) is a common malignancy of the urinary system and represents a serious threat to human health. Although the overall survival of RCC has improved substantially with the development of cancer diagnosis and management, there are various reasons for treatment failure. Firstly, without any readily available biomarkers, timely diagnosis has been greatly hampered. Secondly, the imaging appearance also varies greatly, and its early detection often remains difficult. Thirdly, chemotherapy has been validated as unavailable for treating renal cancer in the clinic due to its intrinsic drug resistance. Concomitant with the progress of nanotechnological methods in pharmaceuticals, the management of kidney cancer has undergone a transformation in the recent decade. Nanotechnology has shown many advantages over widely used traditional methods, leading to broad biomedical applications ranging from drug delivery, prevention, diagnosis to treatment. This review focuses on nanotechnologies in RCC management and further discusses their biomedical translation with the aim of identifying the most promising nanomedicines for clinical needs. As our understanding of nanotechnologies continues to grow, more opportunities to improve the management of renal cancer are expected to emerge.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20–50 nm) and M40 (20–50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe3+ was reduced to Fe2+by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H2O2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V0 of 2.19 ± 0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.

Abstract Objective This study aimed to establish a deep learning method based on convolutional networks for the preliminary study of the pathological diagnosis of prosthetic joint infections (PJI). Methods We enrolled 20 revision patients after joint replacement from the Department of Orthopedics, the First Medical Center, General Hospital of the People's Liberation Army, from January 2021 to January 2022 (10 of whom were confirmed to be infected against 2018 ICM criteria, and the remaining 10 were verified to be non-infected), and classified high-power field images according to 2018 ICM criteria. Then, we inputted 576 positive images and 576 negative images into a neural network by employing a resNET model, used to select 461 positive images and 461 negative images as training sets, 57 positive images and 31 negative images as internal verification sets, 115 positive images and 115 negative images as external test sets. Results The resNET model classification was used to analyze the pathological sections of PJI patients under high magnification fields. The results of internal validation set showed a positive accuracy of 96.49%, a negative accuracy of 87.09%, an average accuracy of 93.22%, an average recall rate 96.49%, and an F1 of 0.9482. The accuracy of external test results was 97.39% positive, 93.04% negative, the average accuracy of external test set was 93.33%, the average recall rate was 97.39%, with an F1 of 0.9482. The AUC area of the intelligent image-reading diagnosis system was 0.8136. Conclusions This study used the convolutional neural network deep learning to identify high-magnification images from pathological sections of soft tissues around joints, against the diagnostic criteria for acute infection, and a high precision and a high recall rate were accomplished. The results of this technique confirmed that better results could be achieved by comparing the new method with the standard strategies in terms of diagnostic accuracy. Continuous upgrading of extended training sets is needed to improve the diagnostic accuracy of the convolutional network deep learning before it is applied to clinical practice.

PurposeThis study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.MethodsThree databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.Results34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.ConclusionThis study’s results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.

Migraine—a disabling neurological disorder, imposes a tremendous burden on societies. To reduce the economic and health toll of the disease, insight into its pathophysiological mechanism is key to improving treatment and prevention. Resting-state functional magnetic resonance imaging (rs-fMRI) studies suggest abnormal functional connectivity (FC) within the default mode network (DMN) in migraine patients. This implies that DMN connectivity change may represent a biomarker for migraine. However, the FC abnormalities appear inconsistent which hinders our understanding of the potential neuropathology. Therefore, we performed a meta-analysis of the FC within the DMN in migraine patients in the resting state to identify the common FC abnormalities. With efficient search and selection strategies, nine studies (published before July, 2022) were retrieved, containing 204 migraine patients and 199 healthy subjects. We meta-analyzed the data using the Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) method. Compared with healthy subjects, migraine patients showed increased connectivity in the right calcarine gyrus, left inferior occipital gyrus, left postcentral gyrus, right cerebellum, right parahippocampal gyrus, and right posterior cingulate gyrus, while decreased connectivity in the right postcentral gyrus, left superior frontal gyrus, right superior occipital gyrus, right orbital inferior frontal gyrus, left middle occipital gyrus, left middle frontal gyrus and left inferior frontal gyrus. These results provide a new perspective for the study of the pathophysiology of migraine and facilitate a more targeted treatment of migraine in the future.

Abstract Objective Previous studies have shown that tumor mutation burden (TMB) in cancer is associated with prognosis. The purpose of this study is to identify TMB related genes in gastric cancer (GC) and to explore their prognostic value. Methods In our research, weighted gene coexpression network analysis (WGCNA) algorithm was used to cluster the most relevant TMB modules in the Cancer Genome Atlas (TCGA) database. Limma package was used to screen the differentially expressed genes, and the intersection was identified as hub genes. We used gene expression profiling interactive analysis (GEPIA) and survival algorithm to analyze the clinical characteristics and prognosis of hub genes in tumor and normal tissue samples of TCGA and Gene Expression Omnibus cohort respectively. We also used CIBERSORT algorithm to calculate the proportion of 22 tumor immune cells in the high and low expression subgroups of hub genes. In addition, we used gene set enrichment analysis (GSEA) to predict the biological function of hub genes. P 1, and mm > 0.8). We found that the expression of SCN7A in tumor tissues was lower than that in normal tissues, and its expression level was also related to overall survival rate and tumor stage. GSEA analysis showed that SCN7A low expression group was enriched with "DNA replication", "base extension repair" and "proteasome" gene sets in GC. In addition, we found that there were significant differences in the infiltration degree of 7 kinds of immune cells between the two groups. Conclusion TMB can indicate the prognosis of gastric cancer. SCN7A is a hub gene associated with TMB, and its low expression is associated with better prognosis.

Abstract Background Suicide is a large and growing public health problem. Little is known about the attributes of suicidal ideation (SI) in the contexts of immigration. This qualitative study aims to explore immigration- and acculturation-related attributes of SI among older immigrants. Methods A qualitative semi-structured interview design. Interview were conducted with 57 older Chinese immigrants in Chicago with self-reported SI in the past month. Results In addition to attributes of SI which have been well documented in the literature, we identified immigration- and acculturation-related attributes, including linguistic and cultural barriers of being integrated to the receiving communities, acculturation gaps in intergenerational support, and uselessness. Conclusions Findings of the study highlight the intersectionality of race, culture, and aging regarding SI, which are essential to improve recognition and understanding of SI among immigrant populations.

Chemotherapy is widely used to treat patients with cancer. However, resistance to chemotherapeutic drugs remains a major clinical concern. The mechanisms of cancer drug resistance are extremely complex and involve such factors such as genomic instability, DNA repair, and chromothripsis. A recently emerging area of interest is extrachromosomal circular DNA (eccDNA), which forms owing to genomic instability and chromothripsis. eccDNA exists widely in physiologically healthy individuals but also arises during tumorigenesis and/or treatment as a drug resistance mechanism. In this review, we summarize the recent progress in research regarding the role of eccDNA in the development of cancer drug resistance as well as the mechanisms thereof. Furthermore, we discuss the clinical applications of eccDNA and propose some novel strategies for characterizing drug-resistant biomarkers and developing potential targeted cancer therapies.

The current evaluation of science and technology projects is mainly completed by peer review, and in the process of evaluation, dividing projects into different groups is a crucial step. Project grouping is challenging due to the small amounts of data, sparsity of features, broad range of subject areas, and the seriously uneven distribution of categories. In this paper, we propose an intelligent automatic grouping method for science and technology projects based on keywords. We expanded the small dataset with samples generated by Paraphrasing, Mixup, and the GPT3 model. The text feature extraction techniques TF-IDF, Word2Vec, and TF-IDF weighted Word2Vec were utilized to pre-process the keywords of projects, and SVM and XGBoost as the classifier. Besides, we used SMOTE to process imbalanced data to alleviate model bias toward minority classes. Experiments show that the project grouping accuracy was substantially improved after introducing the data augmentation method and SMOTE. The combination of Paraphrasing, TF-IDF, SVM and SMOTE achieved the best performance, and the F1 score reached 96.78%, which proves the feasibility of the proposed method.

Abstract Ammonium sulfate ((NH4)2SO4) assisted roasting has been proven to be an effective way to convert spent lithium‐ion battery cathodes to water‐soluble salts. Herein, thermogravimetric (TG) experiments are performed to analyze the mechanism of the sulfation conversion process. First, the reaction activation energies of the sulfate‐assisted roasting are 88.87 and 95.27 kJ mol−1, which are calculated by Kissinger–Akahira–Sunose (KAS) and Flynn–Wall–Ozawa (FWO) methods, respectively. Then, nucleation and growth are determined and verified as the sulfation reaction model by the Šatava–Šesták method. Finally, sub‐reactions of the sulfation process are investigated and reaction controlling mechanisms are determined by the contribution of sub‐reaction. Based on the thermogravimetric analysis, the phase boundary reaction is found to dominate in the initial step of the roasting process (α < 0.6) while the nucleation reaction controlls the following step (α > 0.6), agreeing well with changing trend of activation energy. Overall, thermogravimetric analysis is a general way to study the mechanism of the various roasting processes.

Changes in soil CO2 and N2O emissions due to climate change and nitrogen input will result in increased levels of atmospheric CO2 and N2O, thereby feeding back into Earth’s climate. Understanding the responses of soil carbon and nitrogen emissions mediated by microbe from permafrost peatland to temperature rising is important for modeling the regional carbon and nitrogen balance. This study conducted a laboratory incubation experiment at 15 and 20°C to observe the impact of increasing temperature on soil CO2 and N2O emissions and soil microbial abundances in permafrost peatland. An NH4NO3 solution was added to soil at a concentration of 50 mg N kg−1 to investigate the effect of nitrogen addition. The results indicated that elevated temperature, available nitrogen, and their combined effects significantly increased CO2 and N2O emissions in permafrost peatland. However, the temperature sensitivities of soil CO2 and N2O emissions were not affected by nitrogen addition. Warming significantly increased the abundances of methanogens, methanotrophs, and nirK-type denitrifiers, and the contents of soil dissolved organic carbon (DOC) and ammonia nitrogen, whereas nirS-type denitrifiers, β-1,4-glucosidase (βG), cellobiohydrolase (CBH), and acid phosphatase (AP) activities significantly decreased. Nitrogen addition significantly increased soil nirS-type denitrifiers abundances, β-1,4-N- acetylglucosaminidase (NAG) activities, and ammonia nitrogen and nitrate nitrogen contents, but significantly reduced bacterial, methanogen abundances, CBH, and AP activities. A rising temperature and nitrogen addition had synergistic effects on soil fungal and methanotroph abundances, NAG activities, and DOC and DON contents. Soil CO2 emissions showed a significantly positive correlation with soil fungal abundances, NAG activities, and ammonia nitrogen and nitrate nitrogen contents. Soil N2O emissions showed positive correlations with soil fungal, methanotroph, and nirK-type denitrifiers abundances, and DOC, ammonia nitrogen, and nitrate contents. These results demonstrate the importance of soil microbes, labile carbon, and nitrogen for regulating soil carbon and nitrogen emissions. The results of this study can assist simulating the effects of global climate change on carbon and nitrogen cycling in permafrost peatlands.

BackgroundMedication adherence is the main determinant of effective management of type 2 diabetes, yet there is no gold standard method available to screen patients with high-risk non-adherence. Developing machine learning models to predict high-risk non-adherence in patients with T2D could optimize management.MethodsThis cross-sectional study was carried out on patients with T2D at the Sichuan Provincial People's Hospital from April 2018 to December 2019 who were examined for HbA1c on the day of the survey. Demographic and clinical characteristics were extracted from the questionnaire and electronic medical records. The sample was randomly divided into a training dataset and a test dataset with a radio of 8:2 after data preprocessing. Four imputing methods, five sampling methods, three screening methods, and 18 machine learning algorithms were used to groom data and develop and validate models. Bootstrapping was performed to generate the validation set for external validation and univariate analysis. Models were compared on the basis of predictive performance metrics. Finally, we validated the sample size on the best model.ResultsThis study included 980 patients with T2D, of whom 184 (18.8%) were defined as medication non-adherence. The results indicated that the model used modified random forest as the imputation method, random under sampler as the sampling method, Boruta as the feature screening method and the ensemble algorithms and had the best performance. The area under the receiver operating characteristic curve (AUC), F1 score, and area under the precision-recall curve (AUPRC) of the best model, among a total of 1,080 trained models, were 0.8369, 0.7912, and 0.9574, respectively. Age, present fasting blood glucose (FBG) values, present HbA1c values, present random blood glucose (RBG) values, and body mass index (BMI) were the most significant contributors associated with risks of medication adherence.ConclusionWe found that machine learning methods could be used to predict the risk of non-adherence in patients with T2D. The proposed model was well performed to identify patients with T2D with non-adherence and could help improve individualized T2D management.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.

Summary: How the ataxia telangiectasia mutated (ATM) protein kinase, a core protein in DNA damage response, is regulated at post-transcription level remains unclear. Here it is identified that protein Reprimo (RPRM) downregulates ATM protein levels, resulting in impaired DNA repair and enhanced cellular radiosensitivity. Mechanistically, although primarily localized in the cytoplasm, RPRM translocates to the nucleus shortly after induced by X-irradiation, interacts with ATM and promotes its nuclear export and proteasomal degradation. The RPRM nuclear translocation involves its phosphorylation at serine 98 mediated by cyclin-dependent kinases 4/6 (CDK4/6), and requires Importin-11 (IPO11). Of importance, IPO11-regulated RPRM nuclear import upon irradiation is essential for its regulation on ATM. Thus, RPRM overexpression and its phosphorylation inhibition sensitize cells to genotoxic agents such as irradiation, whereas RPRM deficiency significantly increases resistance to radiation-induced damage both in vitro and in vivo. These findings establish a crucial regulatory mechanism in which ATM is negatively modulated by RPRM.

Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients.Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system.Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%); shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs); increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant.Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.

Background: Fuzi’s compatibilities with other medicines are effective treatments for chronic heart failure. Pre-clinical animal experiments have indicated many possible synergistic compatibility mechanisms of it, but the results were not reliable and reproducible enough. Therefore, we performed this systematic review and meta-analysis of pre-clinical animal studies to integrate evidence, conducted both qualitative and quantitative evaluations of the compatibility and summarized potential synergistic mechanisms.Method: An exhaustive search was conducted for potentially relevant studies in nine online databases. The selection criteria were based on the Participants, Interventions, Control, Outcomes, and Study designs strategy. The SYRCLE risk of bias tool for animal trials was used to perform the methodological quality assessment. RevMan V.5.3 and STATA/SE 15.1 were used to perform the meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions.Result: 24 studies were included in the systematic review and meta-analysis. 12 outcomes were evaluated in the meta-analysis, including BNP, HR, HWI, ALD, LVEDP, LVSP, EF, FS, +dP/dtmax, −dP/dtmax, TNF-α and the activity of Na + -K + -ATPase. Subgroup analyses were performed depending on the modeling methods and duration.Conclusion: The synergistic Fuzi compatibility therapeutic effects against CHF animals were superior to those of Fuzi alone, as shown by improvements in cardiac function, resistance to ventricular remodeling and cardiac damage, regulation of myocardial energy metabolism disorder and RAAS, alleviation of inflammation, the metabolic process in vivo, and inhibition of cardiomyocyte apoptosis. Variations in CHF modeling methods and medication duration brought out possible model–effect and time-effect relationships.

We extracted magnesium-rich calcium phosphate bioceramics from tilapia bone using a gradient thermal treatment approach and investigated their chemical and physicochemical properties. X-ray diffraction showed that tilapia fish bone-derived hydroxyapatite (FHA) was generated through the first stage of thermal processing at 600–800 °C. Using FHA as a precursor, fish bone biphasic calcium phosphate (FBCP) was produced after the second stage of thermal processing at 900–1200 °C. The beta-tricalcium phosphate content in the FBCP increased with an increasing calcination temperature. The fact that the lattice spacing of the FHA and FBCP was smaller than that of commercial hydroxyapatite (CHA) suggests that Mg-substituted calcium phosphate was produced via the gradient thermal treatment. Both the FHA and FBCP contained considerable quantities of magnesium, with the FHA having a higher concentration. In addition, the FHA and FBCP, particularly the FBCP, degraded faster than the CHA. After one day of degradation, both the FHA and FBCP released Mg2+, with cumulative amounts of 4.38 mg/L and 0.58 mg/L, respectively. Furthermore, the FHA and FBCP demonstrated superior bone-like apatite formation; they are non-toxic and exhibit better osteoconductive activity than the CHA. In light of our findings, bioceramics originating from tilapia bone appear to be promising in biomedical applications such as fabricating tissue engineering scaffolds.