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Abstract Background Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. Results Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. Conclusions These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.

Aim: This study aimed to test the predictive power of serum uric acid (UA) levels on new-onset cardiometabolic risk in the Chinese population.Methods: Older people who visited a community health center for a yearly health check (N = 5,000; men: 47%, women: 53%) were enrolled. Participants were followed for 4 years from baseline (median: 48 months), with the endpoints being development of heart failure, atrial fibrillation, diabetes, hypertension, metabolic syndrome, or kidney disease.Results: During follow-up, 342 men (7.4%) and 360 women (8.6%) developed hypertension; 98 men (2.48%) and 135 women (3.06%) developed diabetes; and 175 men (5.04%) and 214 women (4.51%) developed metabolic syndrome. Incident diabetes, hypertension, and metabolic syndrome increased with increased UA levels at baseline (P < 0.001). A multivariate Cox proportional hazards analysis revealed a significant, independent association between the baseline UA level and the onset and future hypertension and/or diabetes in both men and women. However, UA is associated with the development of metabolic syndrome in men, but not in women.Conclusion: UA is an independent predictor of new-onset diabetes and hypertension in both women and men and a predictor of new-onset metabolic syndrome only in men.

Abstract Background and aims Evidence from prospective cohort studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and longitudinal changes in serum ferritin (SF) still limited. This study aimed to investigate the associations of SF baselines and trajectories with new-onset MASLD and to present a MASLD discriminant model. Methods A total of 1895 participants who attended health examinations at least three times in a hospital in Dalian City between 2015 and 2022 were included. The main outcome was the incidence of MASLD. The associations between SF baselines and trajectories with the risk of MASLD were analyzed by Cox proportional hazards regression, restricted cubic spline (RCS) analysis and time-dependent receiver operating characteristic (ROC) curve analysis. In addition, a MASLD discrimination model was established using logistic regression analyses. Results Among the 1895 participants, 492 developed MASLD during follow-up. Kaplan-Meier analysis indicated that participants in the low-stable trajectory group had a longer MASLD-free time compared with participants in other groups. Compared with those in the low-stable trajectory group, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of new-onset MASLD in the medium-high, high-stable and high-high trajectory groups were 1.54(1.18-2.00), 1.77(1.35–2.32) and 1.55(1.07–2.26), respectively (P trend < 0.001). The results were robust in subgroup and sensitivity analyses. Multivariate Cox proportional regression showed that SF was an independent risk factor of MASLD (HR = 1.002, 95%CI: 1.000-1.003, P = 0.003). The restricted cubic spline demonstrated a nonlinear relationship between SF and the risk of MASLD. The 8-variable model had high discriminative performance, good accuracy and clinical effectiveness. The ROC curve results showed that AUC was greater than that of the FLI, HSI and ZJU models (all P

Abstract Background LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. Methods Potential miRNAs binding to the 3ʹ-untranslated region (3ʹ-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. Results LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. Conclusions MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

PurposeThis study aimed to evaluate the effectiveness of generative adversarial networks (GANs) in creating synthetic OCT images as an educational tool for teaching image diagnosis of macular diseases to medical students and ophthalmic residents.MethodsIn this randomized trial, 20 fifth-year medical students and 20 ophthalmic residents were enrolled and randomly assigned (1:1 allocation) into Group real OCT and Group GANs OCT. All participants had a pretest to assess their educational background, followed by a 30-min smartphone-based education program using GANs or real OCT images for macular disease recognition training. Two additional tests were scheduled: one 5 min after the training to assess short-term performance, and another 1 week later to assess long-term performance. Scores and time consumption were recorded and compared. After all the tests, participants completed an anonymous subjective questionnaire.ResultsGroup GANs OCT scores increased from 80.0 (46.0 to 85.5) to 92.0 (81.0 to 95.5) 5 min after training (p

Deep neural network (DNN) -based object detectors have achieved remarkable success, but recent research has revealed their vulnerability to backdoor attacks. The attacks cause the poisoned model to output results normally on benign images, but outputs results specified by the attacker on images inserted with a trigger. Although backdoor attacks have been extensively investigated on image classification tasks, their exploration in object detection tasks remains limited. With the increasing application of object detectors in safety-sensitive fields such as autonomous driving, backdoor attacks on object detection tasks may have serious consequences. Currently, strategies for object disappearance attack scenarios exhibit certain limitations. First, these strategies typically exhibit a one-to-one correspondence, implying that the insertion of one trigger can only result in the disappearance of one object. Second, these strategies typically necessitate the attacker’s knowledge of the object’s precise location information to achieve its disappearance, thereby rendering real-time insertion of triggers unfeasible. Finally, these strategies exhibit diminished attack success rates when applied to two-stage detectors. The paper presents a global object disappearance attack scenario and proposes a simple, covert, and highly effective attack strategy. Experimental evaluations are conducted on four widely-used object detection models (Yolov5s, Yolov8s, Faster R-CNN, and Libra R-CNN) using two benchmark datasets (PASCAL VOC $07+12$ and MS COCO2017) to validate the effectiveness of the proposed strategy. The results demonstrate that the success rate of this attack strategy exceeds 96%, while the poison rate is only 10%.

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. A genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly disruption of two nuclear receptors, Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

Polypoid lesions in the uterus are very common. There are a lot of benign lesions and malignant tumor should be considered. Adenosarcoma, one of the differential diagnoses, is a rare mixed epithelial and mesenchymal tumor consisting of benign epithelial components and sarcoma stroma. Here, we present a case of atypical adenosarcoma that has never been reported. This tumor was composed of benign endometrial epithelium and hyperplastic stroma with extensive bizarre stromal cells. But the cleft-like spaces and papillary stomal fronds which were the typical histological images of adenosarcoma were absent. These stomal cells, including bizarre cells, were positive for vimentin, CD10, ER, PR, cyclin D1 and P16 but were immunonegative for caldesmon. Furthermore, this tumor harbored amplification of MDM2, as revealed by fluorescence in situ hybridization testing (FISH) and next-generation DNA sequencing (NGS).

BackgroundDepression is the most prevalent mental health condition in older adults. However, not all evidence-based treatments are easily accessible. Web-delivered cognitive behavioral therapy (wCBT) facilitated by laypersons is a viable treatment alternative. ObjectiveThis randomized controlled trial aims to evaluate the efficacy of a novel wCBT program, Empower@Home, supported by trained lay coaches, against a waitlist attention control. Empower@Home is among the very few existing wCBT programs specifically designed for older adults. The primary objective was to assess the efficacy of the intervention compared with attention control. The secondary objective was to evaluate the program’s impact on secondary psychosocial outcomes and explore potential change mechanisms. MethodsOlder adults (N=70) were recruited via web-based research registries, social media advertisements, and community agency referrals and randomly assigned to either the intervention or control group in a 1:1 allocation ratio. The intervention group received access to Empower@Home, which included 9 web-delivered self-help lessons and weekly telephone coaching sessions by a trained layperson over 10 weeks. The control group received weekly friendly phone calls and depressive symptom monitoring. The primary clinical outcome was the severity of depressive symptoms assessed using the Patient Health Questionnaire-9. The secondary clinical outcomes included anxiety, anger, social isolation, insomnia, pain intensity, and quality of life. Linear mixed modeling was used to determine the treatment effects on depression, and 2-tailed t tests were used to assess within-group changes and between-group differences. ResultsMost participants in the intervention group completed all 9 sessions (31/35, 89%). The usability and acceptability ratings were excellent. The intervention group had a large within-group change in depressive symptoms (Cohen d=1.22; P

Abstract Purpose Our study aims to discuss glaucoma patients’ needs and Internet habits using big data analysis and Natural Language Processing (NLP) based on deep learning (DL). Methods In this retrospective study, we used web crawler technology to crawl glaucoma-related topic posts from the glaucoma bar of Baidu Tieba, China. According to the contents of topic posts, we classified them into posts with seeking medical advice and without seeking medical advice (social support, expressing emotions, sharing knowledge, and others). Word Cloud and frequency statistics were used to analyze the contents and visualize the keywords of topic posts. Two DL models, Bidirectional Long Short-Term Memory (Bi-LSTM) and Bidirectional Encoder Representations from Transformers (BERT), were trained to identify the posts seeking medical advice. The evaluation matrices included: accuracy, F1 value, and the area under the ROC curve (AUC). Results A total of 10,892 topic posts were included, among them, most were seeking medical advice (N = 7071, 64.91%), and seeking advice regarding symptoms or examination (N = 4913, 45.11%) dominated the majority. The following were searching for social support (N = 2362, 21.69%), expressing emotions (N = 497, 4.56%), and sharing knowledge (N = 527, 4.84%) in sequence. The word cloud analysis results showed that ocular pressure, visual field, examination, and operation were the most frequent words. The accuracy, F1 score, and AUC were 0.891, 0.891, and 0.931 for the BERT model, 0.82, 0.821, and 0.890 for the Bi-LSTM model. Conclusion Social media can help enhance the patient-doctor relationship by providing patients’ concerns and cognition about glaucoma in China. NLP can be a powerful tool to reflect patients’ focus on diseases. DL models performed well in classifying Chinese medical-related texts, which could play an important role in public health monitoring.

Coffee beans, a popular commodity in the world, are processed into coffee, which generates a considerable quantity of spent coffee grounds (SCGs). However, SCGs, a byproduct rich in hemicellulose, poses a challenge due to fermentable sugar loss during conventional pretreatment. This study investigates the efficient production of bioethanol from SCG using an optimized liquid hot water (LHW) pretreatment combined with separate hydrolysis and fermentation (SHF) process. LHW pretreatment at 180 °C for 20 min with a high solid-to-liquid ratio (SLR) of 1:6 (w/v) was optimized to disrupt the lignocellulosic structure and retain high levels of fermentable sugars, which included mannose and glucose. This approach achieved a bioethanol concentration of 15.02 ± 0.05 g/L and a productivity rate of 1.252 g/(L·h), demonstrating the efficiency of this integrated process. Interestingly, the high SLR LHW pretreatment significantly reduces water usage and enhances product concentration, offering a promising, environmentally friendly, and economically viable method for industrial bioethanol production from SCGs without the necessity of detoxification.

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated. Herein, we found that HBO1 expression was elevated in human B-ALL cells and associated with poor disease-free survival. Strikingly, HBO1 knockdown inhibited viability, proliferation, and G1-S cycle progression in B-ALL cells, while provoking apoptosis. In contrast, ectopic overexpression of HBO1 enhanced cell viability and proliferation but inhibited apoptotic activation. The results of in vivo experiments also certificated the inhibitory effect of HBO1 knockdown on tumor growth. Mechanistically, HBO1 acetylated histone H3K14, H4K8, and H4K12, followed by upregulating CTNNB1 expression, resulting in activation of the Wnt/β-catenin signaling pathway. Moreover, a novel small molecule inhibitor of HBO1, WM-3835, potently inhibited the progression of B-ALL. Our data identified HBO1 as an efficacious regulator of CTNNB1 with therapeutic potential in B-ALL.

Equitable and effective planning of urban park green spaces (UPGSs) is an important way to promote green and healthy urban development and improve citizens' quality of life. However, under the background of rapid urbanization, linear large cities, with their unique spatial forms and high-density population agglomerations, have brought special challenges for the planning and management of urban public green spaces. This study takes Lanzhou, a typical representative of high-density linear large cities in China, as a case study. Based on the improvement of the traditional Gaussian Two-Step Floating Catchment Area method (G2SFCA), combined with the Gini coefficient and the Lorentz curve, the social equity and spatial equity of UPGS supply-demand in the central urban area of Lanzhou were evaluated at the city and district scales. Meanwhile, the areas with shortage of UPGS supply-demand were accurately identified as the key areas for future optimization. The results show that: (1) There are significant differences in the equity of UPGS supply-demand in the linear large Lanzhou at the social and spatial levels, and most UPGS resources are enjoyed by a few people; (2) The spatial accessibility of UPGSs has an obvious "string of beads" distribution Characteristics, and the areas with high accessibility are mainly concentrated along rivers; (3) The equity of UPGS supply-demand exhibits a spatial gradient effect, which is characterized by a circle distribution. From the inside to the outside, it is as follows: good supply-dense population, good supply-sparse population, supply shortage-dense population, supply shortage-sparse population. Finally, based on the concept of "progressive micro-regeneration" and the Location Allocation model (LA), the optimal sites for new UPGSs were determined, maximizing the equity of UPGS supply-demand. This provides a practical reference for relevant management departments to optimize park layouts in the future.

BackgroundChatbots have become ubiquitous in our daily lives, enabling natural language conversations with users through various modes of communication. Chatbots have the potential to play a significant role in promoting health and well-being. As the number of studies and available products related to chatbots continues to rise, there is a critical need to assess product features to enhance the design of chatbots that effectively promote health and behavioral change. ObjectiveThis scoping review aims to provide a comprehensive assessment of the current state of health-related chatbots, including the chatbots’ characteristics and features, user backgrounds, communication models, relational building capacity, personalization, interaction, responses to suicidal thoughts, and users’ in-app experiences during chatbot use. Through this analysis, we seek to identify gaps in the current research, guide future directions, and enhance the design of health-focused chatbots. MethodsFollowing the scoping review methodology by Arksey and O'Malley and guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist, this study used a two-pronged approach to identify relevant chatbots: (1) searching the iOS and Android App Stores and (2) reviewing scientific literature through a search strategy designed by a librarian. Overall, 36 chatbots were selected based on predefined criteria from both sources. These chatbots were systematically evaluated using a comprehensive framework developed for this study, including chatbot characteristics, user backgrounds, building relational capacity, personalization, interaction models, responses to critical situations, and user experiences. Ten coauthors were responsible for downloading and testing the chatbots, coding their features, and evaluating their performance in simulated conversations. The testing of all chatbot apps was limited to their free-to-use features. ResultsThis review provides an overview of the diversity of health-related chatbots, encompassing categories such as mental health support, physical activity promotion, and behavior change interventions. Chatbots use text, animations, speech, images, and emojis for communication. The findings highlight variations in conversational capabilities, including empathy, humor, and personalization. Notably, concerns regarding safety, particularly in addressing suicidal thoughts, were evident. Approximately 44% (16/36) of the chatbots effectively addressed suicidal thoughts. User experiences and behavioral outcomes demonstrated the potential of chatbots in health interventions, but evidence remains limited. ConclusionsThis scoping review underscores the significance of chatbots in health-related applications and offers insights into their features, functionalities, and user experiences. This study contributes to advancing the understanding of chatbots’ role in digital health interventions, thus paving the way for more effective and user-centric health promotion strategies. This study informs future research directions, emphasizing the need for rigorous randomized control trials, standardized evaluation metrics, and user-centered design to unlock the full potential of chatbots in enhancing health and well-being. Future research should focus on addressing limitations, exploring real-world user experiences, and implementing robust data security and privacy measures.

Abstract Background Cross breeding is an important way to improve livestock performance. As an important livestock and poultry resource in Henan Province of China, Bohuai goat was formed by crossing Boer goat and Huai goat. After more than 20 years of breeding, BoHuai goats showed many advantages, such as fast growth, good reproductive performance, and high meat yield. In order to better develop and protect Bohuai goats, we sequenced the whole genomes of 30 BoHuai goats and 5 Huai goats to analyze the genetic diversity, population structure and genomic regions under selection of BoHuai goat. Furthermore, we used 126 published genomes of world-wide goat to characterize the genomic variation of BoHuai goat. Results The results showed that the nucleotide diversity of BoHuai goats was lower and the degree of linkage imbalance was higher than that of other breeds. The analysis of population structure showed that BoHuai goats have obvious differences from other goat breeds. In addition, the BoHuai goat is more closely related to the Boer goat than the Huai goat and is highly similar to the Boer goat. Group by selection signal in the BoHuai goat study, we found that one region on chromosome 7 shows a very strong selection signal, which suggests that it could well be the segment region under the intense artificial selection results. Through selective sweeps, we detected some genes related to important traits such as lipid metabolism (LDLR, STAR, ANGPTL8), fertility (STAR), and disease resistance (CD274, DHPS, PDCD1LG2). Conclusion In this paper, we elucidated the genomic variation, ancestry composition, and selective signals related to important economic traits in BoHuai goats. Our studies on the genome of BoHuai goats will not only help to understand the characteristics of the crossbred but also provide a basis for the improvement of cross-breeding programs.

IntroductionEarly stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR.MethodsWe performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID).Results and discussionThe cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

Abstract Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, especially controlling LBG in the long‐term by a single injection. Herein, the pH‐responsive hexa‐histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose‐mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H2O2). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long‐acting hypoglycemic agent with prospective clinical application.

Background: Outdoor physical activity (PA) brings important health benefits, but exposure to polluted air increases health risks. This study aimed to quantify the tradeoff of PA under fine particulate matter (PM2.5) air pollution by estimating the optimal PA duration under various pollution levels. Methods: A risk-benefit analysis was performed to estimate the optimal outdoor moderate-intensity PA (MPA) duration under varying PM2.5 concentrations. Results: An inverse nonlinear relationship was identified between optimal MPA duration and background PM2.5 concentration levels. When background PM2.5 concentration increased to 186 µg/m3, the optimal outdoor MPA duration decreased to 2.5 h/week, the minimum level recommended by current PA guidelines. When background PM2.5 concentration further increased to 235 µg/m3, the optimal outdoor MPA duration decreased to 1 h/week. The relationship between optimal MPA duration and background PM2.5 concentration levels was stronger when exercising at a location closer to a source of air pollution. Compared to the general adult population, adults aged 60 years and older had substantially steeper curves—the optimal outdoor MPA duration decreased to 2.5 h/week when background PM2.5 concentration reached 45 µg/m3. Conclusion: The health benefit of outdoor MPA by far outweighs the health risk of PM2.5 pollution for the global average urban background concentration (22 μg/m3). This modeling study examined a single type of air pollutant and suffered from measurement errors and estimation uncertainties. Future research should examine other air pollutants and indoor PA, incorporate short- and mid-term health effects of MPA and air pollution into the risk-benefit analysis, and provide estimates specific for high-risk subgroups.

Background: Chatbots are computer programs, often built upon large artificial intelligence models, that employ dialogue systems to enable online, natural language conversations with users via text, speech, or both. Body image, broadly defined as a combination of thoughts and feelings about one’s physical appearance, has been implicated in many risk behaviors and health problems, especially among adolescents and young adults. Little is known about how chatbots respond to questions about body image. Methods: This study assessed the responses of 14 widely-used chatbots (eight companion and six therapeutic chatbots) to ten body image-related questions developed upon validated instruments. Chatbots’ responses were documented, with qualities systematically assessed by nine pre-determined criteria. Results: The overall quality of the chatbots’ responses was modest (an average score of five out of nine), with substantial variations in the content and quality of responses across chatbots (individual scores ranging from one to eight). Companion and therapeutic chatbots systematically differed in their responses (e.g., focusing on comforting users vs. trying to identify the causes of negative body image and recommending potential remedies). Some therapeutic chatbots recognized potential mental health crises (self-harm) in test users’ messages. Conclusion: Substantial heterogeneities in the responses were present across chatbots and assessment criteria. Adolescents and young adults struggling with body image could be vulnerable to misleading or biased remarks made by chatbots. Still, the technical and supervision challenges to prevent those adverse consequences remain paramount and unsolved.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder characterized by an enhanced accumulation of lipids, which affects around 40% of the world’s population. The T. fuciformis fungus possesses immunomodulatory activity and other beneficial properties that may alleviate steatosis through a different mechanism. The present study was designed to evaluate the effect T. fuciformis crude polysaccharides (TFCP) on inflammatory and lipid metabolism gene expression, oxidative stress, and lipid profile. Mice were divided into groups receiving (a) a normal chow diet (NCD), (b) a methionine–choline-deficient (MCD) diet, and (c) a MCD diet with TFCP. Liver histopathology was performed, and the hepatic gene expression levels were estimated using qRT-PCR. The lipid profiles, ALT, AST, and efficient oxidative enzymes were analyzed using ELISA. The TFCP administration in the MCD-fed mice suppressed hepatic lipid accumulation, lipid metabolism-associated genes (HMGCR, FABP, SREBP, ACC, and FAS), and inflammation-associated genes (IL-1β, TLR4, TNF-α, and IL-6) whilst enhancing the expression of HNF4α genes. TFCP mitigated against oxidative stress and normalized healthy lipid profiles. These results highlighted that TFCP prevents NAFLD through the inhibition of oxidative stress and inflammation, suggesting TFCP would potentially be an effective therapeutic agent against NAFLD progression.

Deep eutectic solvents (DESs) with a hydrophobic aromatic ring structure offer a promising pretreatment method for the selective delignification of lignocellulosic biomass, thereby enhancing enzymatic hydrolysis. Further investigation is needed to determine whether the increased presence of aromatic rings in hydrogen bond receptors leads to a more pronounced enhancement of lignin removal. In this study, six DES systems were prepared using lactic acid (LA)/acetic acid (AA)/levulinic acid (LEA) as hydrogen bond donors (HBD), along with two independent hydrogen bond acceptors (HBA) (benzyl triethyl ammonium chloride (TEBAC)/benzyl triphenyl phosphonium chloride (BPP)) to evaluate their ability to break down sugarcane bagasse (SCB). The pretreatment of the SCB (raw material) was carried out with the above DESs at 120 °C for 90 min with a solid–liquid ratio of 1:15. The results indicated that an increase in the number of aromatic rings may result in steric hindrance during DES pretreatment, potentially diminishing the efficacy of delignification. Notably, the use of the TEBAC:LA-based DES under mild operating conditions proved highly efficient in lignin removal, achieving 85.33 ± 0.52% for lignin removal and 98.67 ± 2.84% for cellulose recovery, respectively. The maximum digestibilities of glucan (56.85 ± 0.73%) and xylan (66.41 ± 3.06%) were attained after TEBAC:LA pretreatment. Furthermore, the maximum ethanol concentration and productivity attained from TEBAC:LA-based DES-pretreated SCB were 24.50 g/L and 0.68 g/(L·h), respectively. Finally, the comprehensive structural analyses of SCB, employing X-rays, FT-IR, and SEM techniques, provided valuable insights into the deconstruction process facilitated by different combinations of HBDs and HBAs within the DES pretreatment.

BackgroundDepression in older adults has serious biological, psychological, and social consequences. Homebound older adults experience a high burden of depression and significant barriers to accessing mental health treatments. Few interventions to address their specific needs have been developed. Existing treatment modalities can be challenging to scale up, are not tailored to unique population concerns, and require significant staffing support. Technology-assisted, layperson-facilitated psychotherapy has the potential to overcome these challenges. ObjectiveThe aim of this study is to assess the efficacy of a layperson-facilitated internet-delivered cognitive behavioral therapy program tailored for homebound older adults. The novel intervention, Empower@Home, was developed based on user-centered design principles and partnerships between researchers, social service agencies, care recipients, and other stakeholders serving low-income homebound older adults. MethodsThis 2-arm, 20-week pilot randomized controlled trial (RCT) with a waitlist control crossover design aims to enroll 70 community-dwelling older adults with elevated depressive symptoms. The treatment group will receive the 10-week intervention immediately, whereas the waitlist control group will cross over and receive the intervention after 10 weeks. This pilot is part of a multiphase project involving a single-group feasibility study (completed in December 2022). This project consists of a pilot RCT (described in this protocol) and an implementation feasibility study running in parallel with the pilot RCT. The primary clinical outcome of the pilot is the change in depressive symptoms after the intervention and at the 20-week postrandomization follow-up. Additional outcomes include acceptability, adherence, and changes in anxiety, social isolation, and quality of life. ResultsInstitutional review board approval was obtained for the proposed trial in April 2022. Recruitment for the pilot RCT began in January 2023 and is anticipated to end in September 2023. On completion of the pilot trial, we will examine the preliminary efficacy of the intervention on depression symptoms and other secondary clinical outcomes in an intention-to-treat analysis. ConclusionsAlthough web-based cognitive behavioral therapy programs are available, most programs have low adherence and very few are tailored for older adults. Our intervention addresses this gap. Older adults, particularly those with mobility difficulties and multiple chronic health conditions, could benefit from internet-based psychotherapy. This approach can serve a pressing need in society while being cost-effective, scalable, and convenient. This pilot RCT builds on a completed single-group feasibility study by determining the preliminary effects of the intervention compared with a control condition. The findings will provide a foundation for a future fully-powered randomized controlled efficacy trial. If our intervention is found to be effective, implications extend to other digital mental health interventions and populations with physical disabilities and access restrictions who face persistent disparities in mental health. Trial RegistrationClinicalTrials.gov NCT05593276; https://clinicaltrials.gov/ct2/show/NCT05593276 International Registered Report Identifier (IRRID)PRR1-10.2196/44210

The Internet contains a wealth of public opinion on food safety, including views on food adulteration, food-borne diseases, agricultural pollution, irregular food distribution, and food production issues. To systematically collect and analyze public opinion on food safety in Greater China, we developed IFoodCloud, which automatically collects data from more than 3,100 public sources. Meanwhile, we constructed sentiment classification models using multiple lexicon-based and machine learning-based algorithms integrated with IFoodCloud that provide an unprecedented rapid means of understanding the public sentiment toward specific food safety incidents. Our best model’s F1 score achieved 0.9737, demonstrating its great predictive ability and robustness. Using IFoodCloud, we analyzed public sentiment on food safety in Greater China and the changing trend of public opinion at the early stage of the 2019 Coronavirus Disease pandemic, demonstrating the potential of big data and machine learning for promoting risk communication and decision-making.

Straw mulching and N fertilization are effective in augmenting crop yields. Since their combined effects on wheat rhizosphere bacterial communities remain largely unknown, our aim was to assess how the bacterial communities respond to these agricultural measures. We studied wheat rhizosphere microbiomes in a split-plot design experiment with maize straw mulching (0 and 8,000 kg straw ha−1) as the main-plot treatment and N fertilization (0, 120 and 180 kg N ha−1) as the sub-plot treatment. Bacterial communities in the rhizosphere were analyzed using 16S rRNA gene amplicon sequencing and quantitative PCR. Most of the differences in soil physicochemical properties and rhizosphere bacterial communities were detected between the straw mulching (SM) and no straw mulching (NSM) treatments. The contents of soil organic C (SOC), total N (TN), NH4+-N, available N (AN), available P (AP) and available K (AK) were higher with than without mulching. Straw mulching led to greater abundance, diversity and richness of the rhizosphere bacterial communities. The differences in bacterial community composition were related to differences in soil temperature and SOC, AP and AK contents. Straw mulching altered the soil physiochemical properties, leading to greater bacterial diversity and richness of the rhizosphere bacterial communities, likely mostly due to the increase in SOC content that provided an effective C source for the bacteria. The relative abundance of Proteobacteria was high in all treatments and most of the differentially abundant OTUs were proteobacterial. Multiple OTUs assigned to Acidobacteria, Chloroflexi and Actinobacteria were enriched in the SM treatment. Putative plant growth promoters were enriched both in the SM and NSM treatments. These findings indicate potential strategies for the agricultural management of soil microbiomes.

Abstract Tumor-associated macrophages (TAMs), at the core of immunosuppressive cells and cytokines networks, play a crucial role in tumor immune evasion. Increasing evidences suggest that potential mechanisms of macrophage-mediated tumor immune escape imply interpretation and breakthrough to bottleneck of current tumor immunotherapy. Therefore, it is pivotal to understand the interactions between macrophages and other immune cells and factors for enhancing existing anti-cancer treatments. In this review, we focus on the specific signaling pathways through which TAMs involve in tumor antigen recognition disorders, recruitment and function of immunosuppressive cells, secretion of immunosuppressive cytokines, crosstalk with immune checkpoints and formation of immune privileged sites. Furthermore, we summarize correlative pre-clinical and clinical studies to provide new ideas for immunotherapy. From our perspective, macrophage-targeted therapy is expected to be the next frontier of cancer immunotherapy.

Abstract Background The purpose of this study was to implement and evaluate a deep learning (DL) approach for automatically detecting shallow anterior chamber depth (ACD) from two-dimensional (2D) overview anterior segment photographs. Methods We trained a DL model using a dataset of anterior segment photographs collected from Shanghai Aier Eye Hospital from June 2018 to December 2019. A Pentacam HR system was used to capture a 2D overview eye image and measure the ACD. Shallow ACD was defined as ACD less than 2.4 mm. The DL model was evaluated by a five-fold cross-validation test in a hold-out testing dataset. We also evaluated the DL model by testing it against two glaucoma specialists. The performance of the DL model was calculated by metrics, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results A total of 3753 photographs (1720 shallow AC and 2033 deep AC images) were assigned to the training dataset, and 1302 photographs (509 shallow AC and 793 deep AC images) were held out for two internal testing datasets. In detecting shallow ACD in the internal hold-out testing dataset, the DL model achieved an AUC of 0.86 (95% CI, 0.83–0.90) with 80% sensitivity and 79% specificity. In the same testing dataset, the DL model also achieved better performance than the two glaucoma specialists (accuracy of 80% vs. accuracy of 74 and 69%). Conclusions We proposed a high-performing DL model to automatically detect shallow ACD from overview anterior segment photographs. Our DL model has potential applications in detecting and monitoring shallow ACD in the real world. Trial registration http://clinicaltrials.gov , NCT04340635 , retrospectively registered on 29 March 2020.

JNK signaling plays a critical role in both tumor promotion and tumor suppression. Here, we identified clustered microRNAs (miRNAs) miR-306 and miR-79 as novel tumor-suppressor miRNAs that specifically eliminate JNK-activated tumors in Drosophila. While showing only a slight effect on normal tissue growth, miR-306 and miR-79 strongly suppressed growth of multiple tumor models, including malignant tumors caused by Ras activation and cell polarity defects. Mechanistically, these miRNAs commonly target the mRNA of an E3 ubiquitin ligase ring finger protein 146 (RNF146). We found that RNF146 promotes degradation of tankyrase (Tnks), an ADP-ribose polymerase that promotes JNK activation in a noncanonical manner. Thus, downregulation of RNF146 by miR-306 and miR-79 leads to hyper-enhancement of JNK activation. Our data show that, while JNK activity is essential for tumor growth, elevation of miR-306 or miR-79 overactivate JNK signaling to the lethal level via noncanonical JNK pathway and thus eliminate tumors, providing a new miRNA-based strategy against cancer.

To identify therapeutic targets in acute myeloid leukemia (AML), we conducted growth inhibition screens of 2040 small molecules from a library of FDA-approved drugs using a panel of 12 AML cell lines. Tegaserod maleate, a 5-hydroxytryptamine 4 receptor partial agonist, elicits strong anti-AML effects in vitro and in vivo by targeting transient receptor potential melastatin subtype 8 (TRPM8), which plays critical roles in several important processes. However, the role of TRPM8 remains incompletely described in AML, whose treatment is based mostly on antimitotic chemotherapy. Here, we report an unexpected role of TRPM8 in leukemogenesis. Strikingly, TRPM8 knockout inhibits AML cell survival/proliferation by promoting apoptosis. Mechanistically, TRPM8 exerts its oncogenic effect by regulating the ERK–CREB/c-Fos signaling axis. Hyperactivation of ERK signaling can be reversed by TRPM8 inhibition. Importantly, TRPM8 is overexpressed in AML patients, indicating that it is a new prognostic factor in AML. Collectively, our work demonstrates the anti-AML effects of tegaserod maleate via targeting TRPM8 and indicates that TRPM8 is a regulator of leukemogenesis with therapeutic potential in AML.

BackgroundDementia is a global public health priority due to rapid growth of the aging population. As China has the world’s largest population with dementia, this debilitating disease has created tremendous challenges for older adults, family caregivers, and health care systems on the mainland nationwide. However, public awareness and knowledge of the disease remain limited in Chinese society. ObjectiveThis study examines online public discourse and sentiment toward dementia among the Chinese public on a leading Chinese social media platform Weibo. Specifically, this study aims to (1) assess and examine public discourse and sentiment toward dementia among the Chinese public, (2) determine the extent to which dementia-related discourse and sentiment vary among different user groups (ie, government, journalists/news media, scientists/experts, and the general public), and (3) characterize temporal trends in public discourse and sentiment toward dementia among different user groups in China over the past decade. MethodsIn total, 983,039 original dementia-related posts published by 347,599 unique users between 2010 and 2021, together with their user information, were analyzed. Machine learning analytical techniques, including topic modeling, sentiment analysis, and semantic network analyses, were used to identify salient themes/topics and their variations across different user groups (ie, government, journalists/news media, scientists/experts, and the general public). ResultsTopic modeling results revealed that symptoms, prevention, and social support are the most prevalent dementia-related themes on Weibo. Posts about dementia policy/advocacy have been increasing in volume since 2018. Raising awareness is the least discussed topic over time. Sentiment analysis indicated that Weibo users generally attach negative attitudes/emotions to dementia, with the general public holding a more negative attitude than other user groups. ConclusionsOverall, dementia has received greater public attention on social media since 2018. In particular, discussions related to dementia advocacy and policy are gaining momentum in China. However, disparaging language is still used to describe dementia in China; therefore, a nationwide initiative is needed to alter the public discourse on dementia. The results contribute to previous research by providing a macrolevel understanding of the Chinese public’s discourse and attitudes toward dementia, which is essential for building national education and policy initiatives to create a dementia-friendly society. Our findings indicate that dementia is associated with negative sentiments, and symptoms and prevention dominate public discourse. The development of strategies to address unfavorable perceptions of dementia requires policy and public health attention. The results further reveal that an urgent need exists to increase public knowledge about dementia. Social media platforms potentially could be leveraged for future dementia education interventions to increase dementia awareness and promote positive attitudes.

Retinal ganglion cells (RGCs) are the sole output neurons conveying visual stimuli from the retina to the brain, and dysfunction or loss of RGCs is the primary determinant of visual loss in traumatic and degenerative ocular conditions. Currently, there is a lack of RGC-specific Cre mouse lines that serve as invaluable tools for manipulating genes in RGCs and studying the genetic basis of RGC diseases. The RNA-binding protein with multiple splicing (RBPMS) is identified as the specific marker of all RGCs. Here, we report the generation and characterization of a knock-in mouse line in which a P2A-CreERT2 coding sequence is fused in-frame to the C-terminus of endogenous RBPMS, allowing for the co-expression of RBPMS and CreERT2. The inducible Rbpms-CreERT2 mice exhibited a high recombination efficiency in activating the expression of the tdTomato reporter gene in nearly all adult RGCs as well as in differentiated RGCs starting at E13.5. Additionally, both heterozygous and homozygous Rbpms-CreERT2 knock-in mice showed no detectable defect in the retinal structure, visual function, and transcriptome. Together, these results demonstrated that the Rbpms-CreERT2 knock-in mouse can serve as a powerful and highly desired genetic tool for lineage tracing, genetic manipulation, retinal physiology study, and ocular disease modeling in RGCs.

In recent years, the study of urban flood resistance has included the perspectives of spatial environment and multiple elements of urban space, which break through the limitation of only focusing on engineering measures in traditional disaster prevention. The article constructs a flood prevention and mitigation index system under the perspective of resistance based on the basic work of urban physical examination and ignoring the variability of population size affected by floods in different regions. It also takes 6 districts and 6 counties under the jurisdiction of Zhengzhou City as the research object, combines the relevant data of 12 cities, uses the entropy weight method and the coefficient of variation method to determine the index weights comprehensively and introduces the barrier degree diagnosis model. This article carries out urban flood control and disaster reduction special physical examination, considers resistance obstacle factors and promotes strategy analysis and research. The results show that from the perspective of spatial distribution, the flood control and flood mitigation resistance of Zhengzhou City is in a “differential” distribution state and the high resistance areas are Erqi District, Jinshui District and Gongyi City. In general, the resistance index in the southwest region was higher than that in the northeast region and there was a significant difference between urban areas and counties, showing a medium-high and medium-low resistance status. From the results of the study, to improve the level of resistance to flood mitigation in each city, it is necessary to focus on the main obstacle factors that hinder the development of the city and to fundamentally improve the level of resistance to create a more livable and healthier city according to local conditions.

The global express market has expanded significantly in recent years. High-speed rail express freight transportation has been implemented between multiple cities in China, significantly improving transportation efficiency and effectively meeting demand. In this paper, an optimization model for HSR (high-speed railway) express transport plan is constructed using a space-time-state network, and an improved adaptive genetic algorithm is designed to solve the model. Reasonable transport schemes could be arranged for each cargo flow with the objective of maximizing operational revenue. The numerical experiment based on the Harbin–Dalian high-speed railway in China verifies the effectiveness and applicability of the proposed model. The results show that for HSR operators, appropriate transport strategies can be planned in terms of delivery priorities and transportation mode selection to make full use of the remaining capacity of HSR trains and increase operational revenue.

Abstract Haplo-insufficiency of the GATA3 gene causes hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome. Previous studies have shown that Gata3 is required for the development of the prosensory domain and spiral ganglion neurons (SGNs) of the mouse cochlea during embryogenesis. However, its role in supporting cells (SCs) after cell fate specification is largely unknown. In this study, we used tamoxifen-inducible Sox2 CreERT2 mice to delete Gata3 in SCs of the neonatal mouse cochlea and showed that loss of Gata3 resulted in the proliferation of SCs, including the inner pillar cells (IPCs), inner border cells (IBCs), and lateral greater epithelium ridge (GER). In addition, loss of Gata3 resulted in the down-regulation of p27kip1, a cell cycle inhibitor, in the SCs of Gata3-CKO neonatal cochleae. Chromatin immunoprecipitation analysis revealed that GATA3 directly binds to p27 kip1 promoter and could maintain the quiescent state of cochlear SCs by regulating p27 kip1 expression. Furthermore, RNA-seq analysis revealed that loss of Gata3 function resulted in the change in the expression of genes essential for the development and function of cochlear SCs, including Tectb, Cyp26b1, Slitrk6, Ano1, and Aqp4.

Preterm infants are prone to growth and developmental delay, especially social-emotional development. Sensory stimulation may benefit developmental outcomes for these vulnerable infants. This study aims to determine whether 5-integrated sensory stimulation (5-ISS) improves preterm infant social-emotional development. A randomized, parallel trial was conducted from November 2018 to January 2020 at three tertiary hospitals in Kunming, China. Preterm infants were eligible if gestational ages were from 28 to 36 weeks based on ultrasound results when discharged from neonatal wards. Two hundred preterm infants (male n = 110, female n = 90) were randomly allocated to the 5-ISS intervention group (n = 98) and the standard care group (n = 102). Social-emotional development was assessed with the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE). Temperament was assessed with the Infant Behavior Questionnaire-Revised. Anthropometry, which included weight, length, and head circumference, was measured at corrected ages of 1, 3, and 6 months. Demographic and clinical characteristics were similar between the intervention and the standard care groups. At 1- and 3-month corrected age, no significant differences between the two groups were observed in terms of infant development and temperament. At 6 months, significant disparities were found in the social-emotional development scale (mean difference −0.29, 95% CI: −0.58, < -0.001, p = 0.01), infant length (mean difference 0.70, 95% CI: < 0.001, 1.4, p = 0.03), distress to limitation (p = 0.04), and sadness (p = 0.03). A mixed model revealed that the 5-ISS intervention positively affected social-emotional development, length, distress to limitation, and sadness for preterm infants. Integrated sensory stimulation has benefits on social-emotional development, temperament, and length for preterm infants. This program provides a feasible method to promote social-emotional development for preterm infants.

ObjectivesThis study examined the association between childhood adversity and cognitive impairment in later life and explored the potential moderation effect of gender and race.MethodsThe study sample included 15,133 participants of the Health and Retirement Study (1998–2016 surveys) who had complete data on key study measures and were more than 50. The outcome variable is a dichotomous indicator of cognitive impairment as assessed by the Telephone Interview for Cognitive Status for self-respondents and the 16-item Informant Questionnaire on Cognitive Decline in the Elderly for proxies. A total of six childhood adversity indicators included grade retention, parental substance abuse, physical abuse, trouble with the police, moving due to financial hardship, and receipt of help due to financial hardship in early life. The estimation of the association between childhood adversity and cognitive impairment involved Cox proportional hazards regression. Results: Grade retention had the largest effect on incident cognitive impairment (HR = 1.3, 95% CI = 1.23–1.38, p < 0.001), followed by physical abuse by a parent (HR = 1.10, 95% CI = 1.00–1.20, p = 0.001). The impact of grade retention was more detrimental to women than men (interaction term HR = 0.89, 95% CI = 0.80–1.00, p = 0.048, female as the reference). Parental substance abuse was associated with a lower risk of incident cognitive impairment for most racial groups (HR = 0.89, 95% CI = 0.83–0.95, p = 0.001), but this association was reversed in “non-Hispanic other” race, consisting mainly of Asians (HR = 1.54, 95% CI = 1.05–2.26, p = 0.025).DiscussionSome aspects of childhood adversity continue to harm cognitive functioning in later life, while some events may have the opposite effect, with evidence of heterogeneity across gender and race.

Abstract Microbe-mediated ammonia oxidation is a key process in soil nitrogen cycle. However, the effect of maize straw mulching on the ammonia oxidizers in the alkaline purple soil remains largely unknown. A three-year positioning experiment was designed as follows: straw mulching measures as the main-plot treatment and three kinds of nitrogen application as the sub-plot treatment. We found the contents of soil organic carbon (SOC), total nitrogen (TN), available potassium (AK), available nitrogen (AN), available phosphorus (AP), and NH4 +-N were increased after straw mulching and nitrogen application in alkaline purple soil, so did the amoA genes abundance of ammonia-oxidizing archaeal (AOA) and bacterial (AOB). Terminal restriction fragment length polymorphism (T-RFLP) analysis revealed that Thaumarchaeote (448-bp T-RF) was dominated the AOA communities, whereas Nitrosospira sp (111-bp T-RF) dominated the AOB communities. The community compositions of both AOA and AOB were altered by straw mulching and nitrogen application in alkaline purple soil, however, the AOB communities was more responsive than AOA communities to the straw mulching and nitrogen application. Further analysis indicated that SOC and AP were the main factors affecting the abundance and community compositions of AOA and AOB in alkaline purple soil. The present study reported that straw mulching and nitrogen strategies differently shape the soil ammonia oxidizers community structure and abundance, which should be considered when evaluating agricultural management strategies regarding their sustainability and soil quality.

Refined and deodorized camellia oil has been reported to contain a high amount of 3-monochloropropane-1,2-diol esters (3-MCPDE) due to the high-temperature deodorization step. To reduce 3-MCPDE in camellia oil, the physical refining process of camellia oil was simulated on a laboratory scale. Response surface methodology (RSM) was designed to modify and optimize the refining process with five processing parameters (water degumming dosage, degumming temperature, activated clay dosage, deodorization temperature and deodorization time). The optimized new refining approach achieved a 76.9% reduction in 3-MCPDE contents, in which the degumming moisture was 2.97%, the degumming temperature was 50.5 °C, the activated clay dosage was 2.69%, the deodorizing temperature was 230 °C, and the deodorizing time was 90 min. A significance test and analysis of variance results demonstrated that the deodorization temperature and deodorization time contributed significantly to the reduction of 3-MCPD ester. The joint interaction effects of activated clay dosage and deodorization temperature were significant for 3-MCPD ester formation.

Federated learning framework facilitates more applications of deep learning algorithms on the existing network architectures, where the model parameters are aggregated in a centralized manner. However, some of federated learning participants are often inaccessible, such as in a power shortage or dormant state. That will force us to explore the possibility that the parameter aggregation is operated in an ad hoc manner, which is based on consensus computing. On the contrary, since caching mechanism is indispensable to any federated learning mobile node, it is necessary to investigate the connection between it and consensus computing. In this article, we first propose a novel federated learning paradigm, which supports an ad hoc operation mode for federated learning participants. Second, a discrete-time dynamic equation and its control law are formulated to satisfy the demands from federated learning framework, with a quantized caching scheme designed to mask the uncertainties from both asynchronous updates and measurement noises. Then, the consensus conditions and the convergence of the consensus protocol are deduced analytically, and a quantized caching strategy to optimize the convergence speed is provided. Our major contribution is to give the basic theories of distributed consensus problem for federated learning framework, and the theoretical results are validated by numerical simulations.

Nowadays, non-small cell lung cancer (NSCLC) is threatening the health of all mankind. Although many progresses on treatment of lung cancer have been achieved in the past few decades, the current treatment methods are still traditional surgery, radiotherapy, and chemotherapy, which had poor selectivity and side effects. Lower-toxicity and more efficient treatments are in sore need. In this paper, a smart nanodelivery platform based on photothermal therapy, chemotherapy, and immunotherapy was constructed. The nanoparticles are composed of novel photothermal agents, Mn-modified phthalocyanine derivative (MnIIIPC), docetaxel (DTX), and an effective targeting molecule, hyaluronic acid. The nanoplatform could release Mn2+ from MnIIIPC@DTX@PLGA@Mn2+@HA(MDPMH) and probably activate tumor immunity through cGAS-STING and chemotherapy, respectively. Furthermore, DTX could be released in the process for removal of tumor cells. The “one-for-all” nanomaterial may shed some light on treating NSCLC in multiple methods.

Evidence conflicts on the association between sensory difficulty and depression. Few studies have examined this association using longitudinal or population-based data. We used data from Rounds 1–9 of the nationally representative National Health and Aging Trends Study to evaluate the longitudinal association between self-reported visual, hearing, and dual sensory difficulties and clinically significant depressive symptoms. Multivariable Cox regression models were used to evaluate the hazard of incident depressive symptoms. Group-based trajectory modeling identified depressive symptom trajectories (DSTs). Multinomial logistic regression was used to examine the association between sensory status and DSTs. A total of 7,593 participants were included: 56.5% were female, 53.0% were 65–74 years old, 19.0% (95% CI 17.9–20.2%) had hearing, 5.6% (4.9–6.4%) had visual, and 3.3% (2.9–3.8%) had dual sensory difficulties at baseline. Hazard ratios for depressive symptoms in those with visual, hearing, and dual sensory difficulties were 1.25 (95% CI 1.00–1.56, p = 0.047), 0.98 (95% CI 0.82–1.18, p = 0.82), and 1.67 (95% CI 1.29–2.16, p < 0.001), respectively, relative to those without sensory difficulty. A model with four trajectory groups best fit the data. Group 1 (35.8% of the sample, 95% CI: 34.1–37.4) had persistently low risk of depressive symptoms; Group 2 (44.8%, 43.4–46.3) had low but increasing risk; Group 3 (7.1%, 6.2–8.3) had moderate risk; and Group 4 (12.4%, 11.5–13.3) had moderate to high risk that increased. Compared to those without sensory difficulties, individuals with each difficulty were significantly more likely to belong to a group other than Group 1. This study reveals associations between sensory difficulties and mental health that can inform public health interventions.

As a consequence of changing global rainfall patterns, frequent extreme droughts will significantly affect plant growth and ecosystem functions. Fine roots and arbuscular mycorrhizal fungi (AMF) both facilitate Chinese fir nutrient uptake. However, how the growth of fine roots and AMF is regulated for the Chinese fir under drought conditions is unclear. This study used a precipitation reduction treatment (−50% throughfall) to study the seasonal effects of drought on a subtropical Chinese fir plantation. The effects measured included the fine root production, root diameter, specific root length, specific surface area, root tissue density, mycorrhizal hyphal density, spore number, mycorrhizal infection rate and total glomalin. Drought had no significant effect on Chinese fir fine root production but decreased the diameter and tissue density of primary and secondary roots while increasing the specific surface area of secondary roots. Additionally, drought significantly decreased the arbuscular mycorrhizal infection rate and significantly increased hyphal density. The results showed that drought caused the decrease in root diameter, which decreased the surface area available for AMF infection and led to the increase in mycorrhizal hyphal density. Redundancy analyses showed that soil-dissolved organic carbon and nitrogen were the key factors affecting AMF. Our results show that drought could enhance the cooperative strategy of nutrient and moisture absorption by roots and mycorrhizae of the Chinese fir, improving the resistance of Chinese fir growth to drought.

The early stages of mammalian embryonic development involve the participation and cooperation of numerous complex processes, including nutritional, genetic, and epigenetic mechanisms. However, in embryos cultured in vitro, a developmental block occurs that affects embryo development and the efficiency of culture. Although the block period is reported to involve the transcriptional repression of maternal genes and transcriptional activation of zygotic genes, how epigenetic factors regulate developmental block is still unclear. In this study, we systematically analyzed whole-genome methylation levels during five stages of sheep oocyte and preimplantation embryo development using single-cell level whole genome bisulphite sequencing (SC-WGBS) technology. Then, we examined several million CpG sites in individual cells at each evaluated developmental stage to identify the methylation changes that take place during the development of sheep preimplantation embryos. Our results showed that two strong waves of methylation changes occurred, namely, demethylation at the 8-cell to 16-cell stage and methylation at the 16-cell to 32-cell stage. Analysis of DNA methylation patterns in different functional regions revealed a stable hypermethylation status in 3′UTRs and gene bodies; however, significant differences were observed in intergenic and promoter regions at different developmental stages. Changes in methylation at different stages of preimplantation embryo development were also compared to investigate the molecular mechanisms involved in sheep embryo development at the methylation level. In conclusion, we report a detailed analysis of the DNA methylation dynamics during the development of sheep preimplantation embryos. Our results provide an explanation for the complex regulatory mechanisms underlying the embryo developmental block based on changes in DNA methylation levels.

Because images are vulnerable to external attacks in the process of network transmission and traditional image encryption algorithms have limitations such as long encryption time, insufficient entropy or poor diffusion of cipher image information when encrypting color images, a fast image encryption algorithm based on logistics-sine-cosine mapping is proposed. The algorithm first generates five sets of encrypted sequences from the logistics-sine-cosine mapping, then uses the order of the encryption sequence to scramble the image pixels and designs a new pixel diffusion network to further improve the key sensitivity and plain-image sensitivity of the encryption algorithm. Finally, in a series of security analysis experiments, the experimental image Lena was tested 100 times, and the average encryption time was 0.479 s. The average value of the information entropy, pixel change rate and uniform average change intensity of the cipher image reached 7.9994, 99.62% and 33.48%, respectively. The experimental results show that the fast image encryption algorithm based on logistics-sine-cosine mapping takes less time to encrypt, and the cipher image has good information entropy and diffusivity. It is a safe and effective fast image encryption algorithm.

BackgroundDepression is common among homebound older adults. Internet-based cognitive behavioral therapy (iCBT) is a promising but understudied approach for treating depression among older adults with disabilities. ObjectiveThis study aims to understand the experiences of homebound older adults who participated in a pilot feasibility trial of an iCBT for depression. MethodsThe participants included 21 homebound older adults who participated in a generic iCBT program that was not specifically designed for older adults and 8 home care workers who assisted in the iCBT program. Informants completed semistructured individual interviews, which were transcribed verbatim and analyzed using methods informed by grounded theory. A hierarchical code structure of themes and subthemes was developed after an iterative process of constant comparisons and questionings of the initial codes. The data analysis was conducted by using dedoose, a web app for mixed methods research. ResultsThree themes and various subthemes emerged related to participants’ experience of the iCBT intervention, as follows: intervention impact, which involved subthemes related to participants’ perceived impact of the intervention; challenges and difficulties, which involved subthemes on the challenges and difficulties that participants experienced in the intervention; and facilitators, which involved subthemes on the factors that facilitated intervention use and engagement. ConclusionsiCBT is a promising intervention for homebound older adults experiencing depression. Home care workers reported improved relationships with their clients and that the program did not add a burden to their duties. Future programs should involve accessible technical features and age-adapted content to improve user experience, uptake, and adherence. Trial RegistrationClinicalTrials.gov NCT04267289; https://clinicaltrials.gov/ct2/show/NCT04267289

In view of their vast global usage in both consumer products and industrial processes, environmental emission and fates of siloxanes have become concerned issue. This review summarized the research progress, especially in the last decade, on production/consumption data, toxicities, analysis methods, environmental distribution, migration and degradation/transformation of both dimethylsiloxanes and modified siloxanes in atmospheric, aquatic and terrestrial compartments from various areas (especially in China). In spite of their fast degradation (hydrolysis and hydroxylation, etc) in various matrices (except sediment), dimethylsiloxane oligomers have been found in various environmental matrices from many countries due to their constant usage and emission. Moreover, recent literatures have paid attention to behaviors of dimethylsiloxanes in industrial areas, e.g., their higher residual levels compared with residential areas and unique transformed products (such as halogenated products) arose from special industrial production scenarios. Meanwhile, although most prior studies focused on dimethylsiloxanes, identification of modified-siloxanes with other functional groups in environment have been beginning to attract the attention of scientists. Furthermore, related literatures indicated that compared with dimethylsiloxanes, both halogenated-dimethylsiloxanes and modified methylsiloxanes (phenylsiloxanes and trifluoropropylsiloxanes) could have stronger persistence due to their weaker volatilization and degradation, especially in terrestrial matrices.