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Abstract To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Abstract To ensure the successful implementation of the old community renewal project (OCRP), it is essential for the participants to allocate the project risks reasonably. Firstly, this study comprehensively identifies the 20 key risk factors of the OCRP. Secondly, an index system is established from three dimensions to evaluate the risk allocation ability of participants, including a total of nine evaluation indexes. Furthermore, a risk-sharing model based on TOPSIS method and bargaining game model is proposed to determine the optimal risk bearer and risk-taking ratio between the government and the private sector in OCRP. Finally, an OCRP in Chongqing is taken as a case study to verify the applicability of the developed model. The results indicate that in OCRP under PPP mode, the government need to independently bear 7 risks related to politics, law, policy, while the private sector needs to independently bear 8 risks mainly from project financing, design, construction, operation, and maintenance stages. In addition, the risk-taking ratios of 5 risks that require both parties to share are divided. The research findings provide references for ensuring the smooth implementation of urban renewal and sustainable development.

Abstract Background Previous studies have revealed the effects of different physical activity (PA) types on visceral adipose tissue (VAT) accumulation in individuals with overweight/obesity. However, the independent association (especially the dose–response relationship) between PA and VAT in individuals with and without overweight/obesity remains less explored. Visceral adiposity index (VAI), calculated from waist circumference, body mass index (BMI), triglyceride and high-density lipoprotein cholesterol, is a novel indicator of VAT. This study aims to elucidate the association between PA and VAI in participants with and without overweight/obesity. Methods Participants who are overweight or obese and with complete data on VAI, PA, and other essential covariates from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018) were included in this study. PA was evaluated by the PA questionnaire and converted into metabolic equivalent task (MET) hours per week (MET-h/wk) based on the suggested MET scores. Multivariate linear regression models were used to identify the association between PA and VAI. Subgroup analyses, combined with interaction tests and restricted cubic spline (RCS) regression analyses, were utilized to explore the stability and nonlinearity of PA-VAI association, respectively. Results A total of 4, 312 participants with complete data on PA and VAI was included in this study, with 3, 441 of them being overweight or obese. After adjusting for all potential covariates, increased PA was found to be significantly associated with remarkable lower level of VAI in all participants (β = -0.0004, P = 0.003), participants with (β = -0.0013, P = 0.012) and without (β = -0.0004, P = 0.003) overweight/obesity. Subgroup analyses and interaction tests revealed that the PA-VAI association was not modified by other covariates in individuals with overweight/obesity. Furthermore, RCS analyses revealed that PA was significantly, linearly and negatively associated with VAI in all participants, participants with and without overweight/obesity (all P 0.05). Noteworthily, as opposed to individuals without overweight/obesity, PA was significantly associated with lower VAI in participants with overweight/obesity after exceeding the threshold of 150 MET-h/wk. Conclusion Increased PA was significantly associated with lower level of VAI, but a higher level of PA (> 150 MET-h/wk) was needed to obtain significantly lower level of VAI in individuals with overweight/obesity.

Abstract Objective The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations. Methods A total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology‐guided conventional surgical resection (non‐AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology‐guided glioma surgery. Results With NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology‐guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p

The tympanic membrane (TM) is constantly in a state of vibrating. However, there is currently a lack of drug-delivery scaffolds suitable for the dynamic environment of TM perforation. In this study, a mechano-responsive tough hydrogel was developed. It consists of basic fibroblast growth factor (bFGF)-loaded sodium alginate (SA) microspheres, polysulfobetaine methacrylate (polySBMA), and gelatin methacrylate (GelMA). This hydrogel was designed to serve as a TM scaffold to promote perforation healing under dynamic conditions. bFGF was encapsulated in SA microspheres, which were then incorporated into polySBMA-GelMA hydrogels through photo-initiated free radical polymerization. The mechanical properties, tissue adhesiveness, swelling properties, and degradation of the hydrogels were evaluated before and after microsphere incorporation. It was observed that incorporating bFGF-loaded SA microspheres did not significantly impact the adhesion and degradation mechanisms of the hydrogel. The compressive strength and tensile strength of the microsphere-incorporated hydrogel were up to 6.6 MPa and 64.1 kPa, respectively, suitable for a TM scaffold. The release behavior of bFGF from the hydrogel could be controlled by vibration stimulation without significantly affecting the hydrogel's mechanical properties, indicating a mechano-responsive nature of the hydrogel. The in vitro cytotoxicity assay demonstrated that the hydrogels showed no cytotoxic effects. Moreover, cell culture assays demonstrated that vibration stimulation could enhance the release of bFGF, significantly promoting cell proliferation and migration. The results demonstrate the significant potential of the mechano-responsive hydrogel as a scaffold for repairing TM perforations.

Abstract Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all‐cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all‐cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all‐cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all‐cause mortality. During a median follow‐up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high‐TTR and low‐BPV group, the HRs (95% CI) of MACE and all‐cause mortality were 1.309 (1.025–1.671) and 1.842 (1.373–2.473) for the high‐TTR and high‐BPV group, 1.692 (1.347–2.125) and 1.731 (1.298–2.309) for the low‐TTR & low‐BPV group, 2.132 (1.728–2.629) and 2.247 (1.722–2.932) for the low‐TTR & high‐BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all‐cause mortality in patients with hypertension.

Abstract Background Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. Methods Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007–2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. Results A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (β=-8.85, P

Material and structure made by additive manufacturing (AM) have received much attention lately due to their flexibility and ability to customize complex structures. This study first implements multiple objective topology optimization simulations based on a projectile perforation model, and a new topologic projectile is obtained. Then two types of 316L stainless steel projectiles (the solid and the topology) are printed in a selective laser melt (SLM) machine to evaluate the penetration performance of the projectiles by the ballistic test. The experiment results show that the dimensionless specific kinetic energy value of topologic projectiles is higher than that of solid projectiles, indicating the better penetration ability of the topologic projectiles. Finally, microscopic studies (scanning electron microscope and X-ray micro-CT) are performed on the remaining projectiles to investigate the failure mechanism of the internal structure of the topologic projectiles. An explicit dynamics simulation was also performed, and the failure locations of the residual topologic projectiles were in good agreement with the experimental results, which can better guide the design of new projectiles combining AM and topology optimization in the future.

Coastal biological invasions pose a wide-reaching threat to various ecosystems, affecting both vegetation and herbivores in native communities. Although herbivores often exert strong top-down control on vegetation, the impact of invasive species on consumers that strongly regulate native species in invaded ecosystems remains unclear. Therefore, through field surveys and feeding preference experiments, this study examined the effects of the invasive Spartina alterniflora Loisel. (hereafter, Spartina) on the native moth Laelia coenosa Hübner (hereafter, Laelia), a notorious pest that has been documented to cause significant damage to native Phragmites australis (Cav.) Trin. ex Steud. (hereafter, Phragmites) marshes in coastal wetlands of China. Field surveys showed that Laelia larvae were more abundant and had higher grazing rates in Phragmites than in Spartina marshes in summer, but these patterns reversed in autumn. Feeding experiments consistently showed that the dietary preference of Laelia larvae switched from Phragmites in summer to Spartina in autumn, likely because Spartina has a longer growing season and relatively higher nutritional quality than Phragmites in autumn. Thus, by providing shelters (i.e., dietary sources and habitats) during unfavorable seasons, Spartina invasions may facilitate this insect pest Laelia and potentially amplify its damage to native wetland vegetation. Our work reveals a novel, indirect mechanism of coastal invasion impacts and highlights the importance of incorporating seasonal variation in plant-herbivore interactions.

Tympanic membrane perforation (TMP) is one of the most common conditions in otolaryngology worldwide, and hearing damage caused by inadequate or prolonged healing can be distressing for patients. This article examines the rationale for utilizing three-dimensional (3D) printing to produce scaffolds for repairing TMP, compares the advantages and disadvantages of 3D printed and bioprinted grafts with traditional autologous materials and other tissue engineering materials in TMP repair, and highlights the practical and clinical significance of 3D printing in TMP repair while discussing the current progress and promising future of 3D printing and bioprinting. There is a limited number of reviews specifically dedicated to 3D printing for TMP repair. The majority of reviews offer a general overview of the applications of 3D printing in the broader realm of tissue regeneration, with some mention of TMP repair. Alternatively, they explore the biopolymers, cells, and drug molecules utilized for TMP repair. However, more in-depth analysis is needed on the strategies for selecting bio-inks that integrate biopolymers, cells, and drug molecules for tympanic membrane repair.

Abstract Mechanoluminescence (ML) sensing technologies open up new opportunities for intelligent sensors, self-powered displays and wearable devices. However, the emission efficiency of ML materials reported so far still fails to meet the growing application requirements due to the insufficiently understood mechano-to-photon conversion mechanism. Herein, we propose to quantify the ability of different phases to gain or lose electrons under friction (defined as triboelectric series), and reveal that the inorganic-organic interfacial triboelectricity is a key factor in determining the ML in inorganic-organic composites. A positive correlation between the difference in triboelectric series and the ML intensity is established in a series of composites, and a 20-fold increase in ML intensity is finally obtained by selecting an appropriate inorganic-organic combination. The interfacial triboelectricity-regulated ML is further demonstrated in multi-interface systems that include an inorganic phosphor-organic matrix and organic matrix-force applicator interfaces, and again confirmed by self-oxidization and reduction of emission centers under continuous mechanical stimulus. This work not only gives direct experimental evidences for the underlying mechanism of ML, but also provides guidelines for rationally designing high-efficiency ML materials.

Aggressive behavior is an important indicator of chicken welfare assessment. At present, the aggressive behavior of chickens typically requires human observation for welfare assessment, and the assessment results are influenced by the subjective judgment of humans. This paper proposes an aggressive chicken behavior identification method based on a hybrid strategy improved Sparrow Search Algorithm combined with Support Vector Machine (ISSA-SVM). Nine-axis inertial sensors were used to collect the behavioral data of chickens. A total of 231-dimensional feature data in the time and frequency domains of the behavioral data were extracted through a 1 s sliding window. To reduce feature redundancy, the initial population is initialized using circle chaotic mapping instead of random initialization of the original sparrow algorithm to increase the uniformity of the initial population distribution in the feature space; adaptive weights are introduced to increase the search range of the early iteration, and the global optimal solution of the previous generation is introduced to improve the global search capability of the algorithm; the optimal solution is perturbed using the dimension-by-dimension mutation strategy of adaptive t-distribution to increase the diversity of the feature distribution. ISSA-SVM reduced the feature dimensionality from 231 to 17, indicating a reduction of 92.6%. The recognition overall accuracy of ISSA-SVM for aggressive chicken behavior was 94.27%, which improved by 1.33% compared to SVM. The results of the experiment show that of all the aggressive chicken behaviors during the 5-day experiment, fighting behavior occurred most frequently from 11:00 to 13:00 and from 17:00 to 18:00. This study provides a method for the automatic identification of aggressive chicken behavior and can serve as an informational tool for poultry welfare assessment.

There is no doubt that when solid surfaces are modified, the functional groups and atoms directly bonded to solid atoms play a major role in adsorption interactions with molecules or resins. In this study, the adhesion and dissociation between epoxy resin and molecules containing Si atoms were analyzed. The analysis, conducted in contact with the solid surface of silicon, utilized quantum chemical calculations based on a molecular model. We compared some Si-containing molecular models to test quantum chemical calculations that contribute to the study of adhesion and dissociation between epoxy resins and solid surfaces somehow other than simple potential energy curve calculations. The AFIR (artificial force induced reaction) method, implemented in the GRRM (global reaction route mapping) program, was employed to separate an epoxy resin model molecule and three types of silicon compounds (Si(CH3)2(OH)2, Si(CH3)4, and (CH3)2SiF2) in three directions, determining their minimum dissociation energy when changing the applied energy by 2.5 kJ/mol. In systems with weak hydrogen bonds, such as Si(CH3)4 or (CH3)2SiF2, the energy required for dissociation was not large; however, in systems with strong hydrogen bonds, such as Si(CH3)2(OH)2, dissociation was more difficult in the vertical direction. Although anisotropy due to hydroxyl groups was calculated in the horizontal direction, dissociation remained relatively easy.

Background: The clinical characteristics and risk factors of all-cause mortality in young hospitalized patients with comorbid coronary heart disease and hypertension (CAD + HT) are not well-characterized. Method: A total of 2288 hospitalized CAD patients (age

Despite the proliferation of education technologies (EdTech) in education, past reviews that examine their effectiveness in the context of low- and middle-income countries are few and rarely seek to include studies published in languages other than English. This systematic review investigates the effectiveness of EdTech on primary and secondary student learning outcomes in China via a systematic search of both English- and Chinese-language databases. Eighteen (18) unique studies in 21 manuscripts on the effectiveness of EdTech innovations in China met the eligibility criteria. The majority of these evaluate computer aided self-led learning software packages designed to improve student learning (computer assisted learning, CAL), while the rest evaluate the use of EdTech to improve classroom instruction (ICI) and remote instruction (RI). The pooled effect size of all included studies indicates a small, positive effect on student learning (0.13 SD, 95% CI [0.10, 0.17]). CAL used a supplement to existing educational inputs – which made up the large majority of positive effect sizes – and RI programs consistently showed positive and significant effects on learning. Our findings indicate no significant differences or impacts on the overall effect based on moderating variables such as the type of implementation approach, contextual setting, or school subject area. Taken together, while there is evidence of the positive impacts of two kinds of EdTech (supplemental computer assisted learning and remote instruction) in China, more evidence is needed to determine the effectiveness of other approaches.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well-characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR

Summary: Plant pathogens manipulate host development, facilitating colonization and proliferation. Ralstonia solanacearum is a soil-borne bacterial pathogen that penetrates roots and colonizes plants through the vascular system, causing wilting and death. Here, we find that RipAC, an effector protein from R. solanacearum, alters root development in Arabidopsis, promoting the formation of lateral roots and root hairs. RipAC interacts with CELLULOSE SYNTHASE (CESA)-INTERACTIVE PROTEIN 1 (CSI1), which regulates the activity of CESA complexes at the plasma membrane. RipAC disrupts CESA-CSI1 interaction, leading to a reduction in cellulose content, root developmental alterations, and a promotion of bacterial pathogenicity. We find that CSI1 also associates with the receptor kinase FERONIA, forming a complex that negatively regulates immunity in roots; this interaction, however, is not affected by RipAC. Our work reveals a bacterial virulence strategy that selectively affects the activities of a host target, promoting anatomical alterations that facilitate infection without causing activation of immunity.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Background: Physical activity (PA) is widely recommended for preventing and combating obesity, but the most effective PA pattern for treating obesity remains unclear. Cardiometabolic index (CMI), derived from waist height ratio and triglycerides to high-density lipoprotein-cholesterol ratio, is a novel indicator for evaluating obesity. However, the relationship between different PA patterns and CMI remains unelucidated. Objective: This study aimed to explore the association between different PA patterns and CMI in U.S. adults. Methods: Participants with complete information in CMI, PA patterns, and other covariates in the National Health and Nutrition Examination Survey database (2007–2016) were included in this study. Multivariate linear regression models were utilized to explore the relationship between PA patterns and CMI. Moreover, stratified analyses, interaction tests and restricted cubic spline (RCS) regression analysis were used to investigate the stability and nonlinearity of the association, respectively. Results: A total of 16,442 adults were included in this study. After adjusting for all potential covariates, only the regularly active group was significantly associated with CMI reduction (β = −0.13, 95% CI: 0.19 to −0.07, P 60, with higher education level, and who are current drinkers. Furthermore, RCS analysis indicated that total PA in a week was significantly, nonlinearly associated with CMI in non-inactive adults, and that a total of PA more than 330 min can reap favorable CMI reduction. Conclusion: Being regularly active is associated with significant CMI reduction, while being weekend warriors and insufficiently active do not achieve equivalent benefits. For non-inactive individuals, engaging in PA for more than 330 min weekly helps to reduce CMI effectively.

Homalotylus tianjinensis Zu, sp. nov., H. bicolor Zu, sp. nov. and H. guangxiensis Zu, sp. nov. are described as new to science; H. agarwali Anis & Hayat, 1998, H. hemipterinus (De Stefani, 1898) and H. varicolorus Krishnachaitanya & Manickavasagam, 2016 are newly recorded from China. A key to Chinese species based on females is also presented.

Investigation of molten salts structure will benefit its’ application in molten salts reactor, spent fuel reprocessing and concentrating solar power plant. This manuscript summarized previous researches concerning the short-range and intermediate-range structure of molten salts. The major existence form of cations, the average coordination number, distribution of coordination number, the distribution of ion distance, the cation-anion alternation, the anion-sharing network in molten salts are discussed in this article. It also addresses the origin of peaks in structure function that are obtained from X-ray scattering and neutron scattering experiments. Finally, this paper discusses the feature works that can be done in this research field.

Abstract Programmable metasurfaces present significant capabilities in manipulating electromagnetic waves, making them a promising candidate for simultaneous wireless information and power transfer (SWIPT), which has the potential to enable sustainable wireless communication in complex electromagnetic environments. However, challenges remain in terms of maximum power transmission distance and stable phase manipulation with high-power scattered waves. Additionally, waveform limitations restrict average scattered power and rectifier conversion efficiency, affecting data transmission rates and energy transmission distance. Here we show an amplifying programmable metasurface (APM) and a joint modulation method to address these challenges. The APM mitigates the peak-to-average power ratio and improves maximum power, phase response stability, average output power, and rectifier conversion efficiency. Through experimental validation, we demonstrate the feasibility of the SWIPT system, showcasing simultaneous LED array powering and movie video transmission. This innovative SWIPT system holds promise for diverse applications, including 6 G wireless communications, IoT, implanted devices, and cognitive radio networks.

Abstract Millimetre‐wave radar offers high ranging accuracy and can capture subtle vibration information of the human heart. This study proposes a heartbeat prediction method based on the transformer model using millimetre‐wave radar. Firstly, the millimetre‐wave radar was used to collect the heartbeat data and conduct normalisation processing. Secondly, a position coding was introduced to assign sine or cosine variables to input data and extract their relative position relationship. Subsequently, the transformer encoder was adopted to allocate attention to input data through the multi‐head attention mechanism, using a mask layer before the decoding layer to prevent the leakage of future information. Finally, we employ the fully connected layer was employed in the linear decoder for regression and output the predicted results. Our experimental results demonstrate that the proposed transformer model achieves nearly 30% higher prediction accuracy than traditional long short‐term memory models while improving both the prediction accuracy and convergence rate. The proposed method has great potential in predicting the heartbeat state of elderly and sick patients.

Abstract Background The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. Results We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). Conclusions Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy. Graphical abstract

Inorganic trivalent arsenic (iAsⅢ) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsⅢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsⅢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsⅢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsⅢ. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the β-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient β-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsⅢ in female adult offspring partially through epigenetic reprogramming of the β-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.

Food fraud is widespread in the aquatic food market, hence fast and non-destructive methods of identification of fish flesh are needed. In this study, multispectral imaging (MSI) was used to screen flesh slices from 20 edible fish species commonly found in the sea around Yantai, China, by combining identification based on the mitochondrial COI gene. We found that nCDA images transformed from MSI data showed significant differences in flesh splices of the 20 fish species. We then employed eight models to compare their prediction performances based on the hold-out method with 70% training and 30% test sets. Convolutional neural network (CNN), quadratic discriminant analysis (QDA), support vector machine (SVM), and linear discriminant analysis (LDA) models perform well on cross-validation and test data. CNN and QDA achieved more than 99% accuracy on the test set. By extracting the CNN features for optimization, a very high degree of separation was obtained for all species. Furthermore, based on the Gini index in RF, 11 bands were selected as key classification features for CNN, and an accuracy of 98% was achieved. Our study developed a successful pipeline for employing machine learning models (especially CNN) on MSI identification of fish flesh, and provided a convenient and non-destructive method to determine the marketing of fish flesh in the future.

Background Cardiac conduction diseases can lead to life‐threatening outcomes. However, the evidence on risk factors for conduction disease that is needed to underpin prevention strategies is limited. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases. Methods and Results This study included 101 080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until December 31, 2020. During follow‐up, 14 397 participants were diagnosed as having type 2 diabetes. For each case subject, 1 control subject was randomly selected, matched for age (±1 year) and sex. The final analysis comprised 10 744 case‐control pairs. Cox regression models with age as the underlying time scale were used. During a median follow‐up of 5.46 years, 571 incident events occurred, including 164 atrioventricular blocks, 414 bundle‐branch blocks (BBBs), 274 right BBBs, and 210 left BBBs. After adjustment for potential confounders, participants with type 2 diabetes diagnosed had greater relative risks for most outcomes relative to controls, with hazard ratios of 1.42 (95% CI, 1.18–1.67) for conduction diseases, 1.40 (95% CI, 1.00–1.96) for atrioventricular blocks, 1.43 (95% CI, 1.16–1.75) for BBBs, and 1.69 (95% CI, 1.15–2.49) for left BBBs. In contrast, no association between diabetes and right BBB was observed. Conclusions In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease but not associated with the development of right BBB.

Abstract Objective: To examine Hb level and anaemia status among infants under 6 months of age in rural China. Design: A cross-sectional survey collected data among infants under 6 months and their primary caregivers in Sichuan, China. Anaemia was defined using both the WHO and China Pediatrics Association thresholds. Multivariable linear regression was used to identify relevant factors among two age groups (

Abstract. Background:. The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF. Methods:. This cross-sectional study was conducted in Chinese People's Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD. Results:. The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of

Abstract Objectives Identifying prognostic factors helps optimize the treatment regimen and promote favorable outcomes. We conducted a prospective cohort study on patients with pulmonary tuberculosis to construct a clinical indicator-based model and estimate its performance. Methods We performed a two-stage study by recruiting 346 pulmonary tuberculosis patients diagnosed between 2016 and 2018 in Dafeng city as the training cohort and 132 patients diagnosed between 2018 and 2019 in Nanjing city as the external validation population. We generated a risk score based on blood and biochemistry examination indicators by the least absolute shrinkage and selection operator (LASSO) Cox regression. Univariate and multivariate Cox regression models were used to assess the risk score, and the strength of association was expressed as the hazard ratio (HR) and 95% confidence interval (CI). We plotted the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC). Internal validation was conducted by 10-fold cross-validation. Results Ten significant indicators (PLT, PCV, LYMPH, MONO%, NEUT, NEUT%, TBTL, ALT, UA, and Cys-C) were selected to generate the risk score. Clinical indicator-based score (HR: 10.018, 95% CI: 4.904–20.468, P

Abstract Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to “withstand setbacks, adapt positively, and bounce back from adversity” on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. Methods The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. Results From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00–2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18–29 years; adjusted odds ratio [aOR] = 0.31–0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34–2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62–3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19–2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59–3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62–9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72–54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56–7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09–2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72–4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09–3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90–4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57–4.10). Conclusions We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes.

Abstract Background The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors. Methods In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively. Results The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%. Conclusions This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.

Abstract Background Intratumoral heterogeneity is the primary challenge in the treatment of glioblastoma (GBM). The presence of glioma stem cells (GSCs) and their conversion between different molecular phenotypes contribute to the complexity of heterogeneity, culminating in preferential resistance to radiotherapy. ARP2/3 (actin-related protein-2/3) complexes (ARPs) are associated with cancer migration, invasion and differentiation, while the implications of ARPs in the phenotype and resistance to radiotherapy of GSCs remain unclear. Methods We screened the expression of ARPs in TCGA-GBM and CGGA-GBM databases. Tumor sphere formation assays and limiting dilution assays were applied to assess the implications of ARPC1B in tumorigenesis. Apoptosis, comet, γ-H2AX immunofluorescence (IF), and cell cycle distribution assays were used to evaluate the effect of ARPC1B on radiotherapy resistance. Immunoprecipitation (IP) and mass spectrometry analysis were used to detect ARPC1B-interacting proteins. Immune blot assays were performed to evaluate protein ubiquitination, and deletion mutant constructs were designed to determine the binding sites of protein interactions. The Spearman correlation algorithm was performed to screen for drugs that indicated cell sensitivity by the expression of ARPC1B. An intracranial xenograft GSC mouse model was used to investigate the role of ARPC1B in vivo. Results We concluded that ARPC1B was significantly upregulated in MES-GBM/GSCs and was correlated with a poor prognosis. Both in vitro and in vivo assays indicated that knockdown of ARPC1B in MES-GSCs reduced tumorigenicity and resistance to IR treatment, whereas overexpression of ARPC1B in PN-GSCs exhibited the opposite effects. Mechanistically, ARPC1B interacted with IFI16 and HuR to maintain protein stability. In detail, the Pyrin of IFI16 and RRM2 of HuR were implicated in binding to ARPC1B, which counteracted TRIM21-mediated degradation of ubiquitination to IFI16 and HuR. Additionally, the function of ARPC1B was dependent on IFI16-induced activation of NF-κB pathway and HuR-induced activation of STAT3 pathway. Finally, we screened AZD6738, an ataxia telangiectasia mutated and rad3-related (ATR) inhibitor, based on the expression of ARPC1B. In addition to ARPC1B expression reflecting cellular sensitivity to AZD6738, the combination of AZD6738 and radiotherapy exhibited potent antitumor effects both in vitro and in vivo. Conclusion ARPC1B promoted MES phenotype maintenance and radiotherapy resistance by inhibiting TRIM21-mediated degradation of IFI16 and HuR, thereby activating the NF-κB and STAT3 signaling pathways, respectively. AZD6738, identified based on ARPC1B expression, exhibited excellent anti-GSC activity in combination with radiotherapy.

Background: MicroRNA-216a-5p (miR-216a-5p) mediates inflammatory responses and neuronal injury to participate in the pathology of spinal cord injury (SCI). This study intended to explore the engagement of bone marrow mesenchymal stem cell exosomes (BMSC-Exo)-derived miR-216a-5p in locomotor performance, neuronal injury, and microglia-mediated inflammation in SCI rats.Methods: Rat BMSC or BMSC-Exo was injected into SCI rats. GW4869 treatment was adopted to suppress the exosome secretion from BMSC. Subsequently, miR-216a-5p-overexpressed BMSC-Exo (BMSC-miR-Exo) or negative-control-overexpressed BMSC-Exo (BMSC-NC-Exo) were injected into SCI rats.Results: The injection of BMSC or BMSC-Exo enhanced locomotor performance reflected by Basso, Beattie & Bresnahan score (p < 0.001), and neuronal viability reflected by NeuN+ cells (p < 0.01), but attenuated neuronal apoptosis reflected by TUNEL positive rate, cleaved-caspase-3 expression, and B-cell leukemia/lymphoma-2 expression (p < 0.05). Additionally, the injection of BMSC or BMSC-Exo suppressed microglia M1 polarization-mediated inflammation reflected by IBA1+iNOS+ cells, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 (p < 0.01). Notably, the effect of BMSC on the above functions was retarded by the GW4869 treatment (most p < 0.05). Subsequently, the injection of BMSC-miR-Exo further improved locomotor performance (p < 0.05), while inhibiting neuronal apoptosis (p < 0.05) and microglia M1 polarization-mediated inflammation (p < 0.05) compared to BMSC-NC-Exo. Interestingly, the injection of BMSC-miR-Exo reduced toll-like receptor 4 (TLR4) (p < 0.01), myeloid differentiation factor 88 (p < 0.05), and nuclear factor kappa B (NF-κB) (p < 0.05) expressions versus BMSC-NC-Exo.Conclusion: BMSC-Exo-derived miR-216a-5p enhances functional recovery by attenuating neuronal injury and microglia-mediated inflammation in SCI, which may be attributable to its inhibition of the TLR4/NF-κB pathway.

Responsive photonic crystals (PCs) with bio-inspired microstructures and tailorable functionalities are of critical importance for their potential applications in diverse fields such as biological detection, sensing, decoration, anti-counterfeiting, etc. However, limited by preparation technologies and design theories, it is still a challenge to accurately and uniformly deposit smart responsive materials on natural PC structures and achieve dual stimulus response. Herein, a simple and rapid in situ polymerization method is presented for preparing dual-responsive PCs with ultra-precise micro-/nanoscale hierarchical structures. Exposure of the reaction site by deacetylation of Morpho butterfly wings allows in situ polymerisation of poly (N-isopropylacrylamide-co-acrylic acid) (P(NIPAAM-co-AAc)) on the surface of the natural photonic structure. The obtained P(NIPAAM-co-AAc) photonic crystals (P(NIPAAM-co-AAc)-PCs) exhibited a dual response to pH and temperature reversibility. In addition, the synergistic effect of the structures and materials on the optical response of the natural PCs is revealed. This work allows the combination of natural hierarchical PC structures with smart hydrogel to achieve an optical response to pH and temperature, thus opening up the channels for responsive PC to multiple stimulus responses.

The effects of surface roughness on the corrosion mechanism of HP-13Cr stainless steel in the dynamic aggressive oilfield environment were investigated through surface analysis, weight-loss measurements, and computational fluid dynamics simulations. The results showed that the surface roughness mainly changed the fluid state at the metal/solution interface. With the increase in the surface roughness, the vortex was more likely to form at the trough of the waves. The vortex could result in the deposition process and inhomogeneity in the thickness of the oxide film. The pitting corrosion occurred more easily. Furthermore, the temperature and CO2 pressure obviously facilitated the corrosion rate.

Abstract Background The prevalence of infectious diseases remains one of the major challenges faced by the Chinese health sector. Policymakers have a tremendous interest in investigating the spatiotemporal epidemiology of infectious diseases. We aimed to review the small-scale (city level, county level, or below) spatiotemporal epidemiology of notifiable infectious diseases in China through a systematic review, thus summarizing the evidence to facilitate more effective prevention and control of the diseases. Methods We searched four English language databases (PubMed, EMBASE, Cochrane Library, and Web of Science) and three Chinese databases (CNKI, WanFang, and SinoMed), for studies published between January 1, 2004 (the year in which China’s Internet-based disease reporting system was established) and December 31, 2021. Eligible works were small-scale spatial or spatiotemporal studies focusing on at least one notifiable infectious disease, with the entire territory of mainland China as the study area. Two independent reviewers completed the review process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results A total of 18,195 articles were identified, with 71 eligible for inclusion, focusing on 22 diseases. Thirty-one studies (43.66%) were analyzed using city-level data, 34 (47.89%) were analyzed using county-level data, and six (8.45%) used community or individual data. Approximately four-fifths (80.28%) of the studies visualized incidence using rate maps. Of these, 76.06% employed various spatial clustering methods to explore the spatial variations in the burden, with Moran’s I statistic being the most common. Of the studies, 40.85% explored risk factors, in which the geographically weighted regression model was the most commonly used method. Climate, socioeconomic factors, and population density were the three most considered factors. Conclusions Small-scale spatiotemporal epidemiology has been applied in studies on notifiable infectious diseases in China, involving spatiotemporal distribution and risk factors. Health authorities should improve prevention strategies and clarify the direction of future work in the field of infectious disease research in China.

Abstract Background Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed. Methods We performed a comprehensive analysis of TMSs and thymosin β10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays. Results We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma. Conclusion These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients.

Abstract Background Resistance to temozolomide (TMZ) is a major obstacle to preventing glioblastoma (GBM) recurrence after surgery. Although long noncoding RNAs (lncRNAs) play a variety of roles in GBM, the lncRNAs that regulate TMZ resistance have not yet been clearly elucidated. This study aims to identify lncRNAs that may affect TMZ treatment sensitivity and to explore novel therapeutic strategies to overcome TMZ resistance in GBM. Methods LncRNAs associated with TMZ resistance were identified using the Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) datasets. Quantitative real-time PCR (qRT–PCR) was used to determine the expression of PDIA3P1 in TMZ-resistant and TMZ-sensitive GBM cell lines. Both gain-of-function and loss-of-function studies were used to assess the effects of PDIA3P1 on TMZ resistance using in vitro and in vivo assays. Glioma stem cells (GSCs) were used to determine the effect of PDIA3P1 on the GBM subtype. The hypothesis that PDIA3P1 promotes proneural-to-mesenchymal transition (PMT) was established using bioinformatics analysis and functional experiments. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to examine the interaction between PDIA3P1 and C/EBPβ. The posttranslational modification mechanism of C/EBPβ was verified using ubiquitination and coimmunoprecipitation (co-IP) experiments. CompuSyn was leveraged to calculate the combination index (CI), and the antitumor effect of TMZ combined with nefllamapimod (NEF) was validated both in vitro and in vivo. Results We identified a lncRNA, PDIA3P1, which was upregulated in TMZ-resistant GBM cell lines. Overexpression of PDIA3P1 promoted the acquisition of TMZ resistance, whereas knockdown of PDIA3P1 restored TMZ sensitivity. PDIA3P1 was upregulated in MES-GBM, promoted PMT progression in GSCs, and caused GBMs to be more resistant to TMZ treatment. Mechanistically, PDIA3P1 disrupted the C/EBPβ-MDM2 complex and stabilized the C/EBPβ protein by preventing MDM2-mediated ubiquitination. Expression of PDIA3P1 was upregulated in a time- and concentration-dependent manner in response to TMZ treatment, and TMZ-induced upregulation of PDIA3P1 was mediated by the p38α-MAPK signaling pathway. NEF is a small molecule drug that specifically targets p38α with excellent blood–brain barrier (BBB) permeability. NEF blocked TMZ-responsive PDIA3P1 upregulation and produced synergistic effects when combined with TMZ at specific concentrations. The combination of TMZ and NEF exhibited excellent synergistic antitumor effects both in vitro and in vivo. Conclusion PDIA3P1 promotes PMT by stabilizing C/EBPβ, reducing the sensitivity of GBM cells to TMZ treatment. NEF inhibits TMZ-responsive PDIA3P1 upregulation, and NEF combined with TMZ provides better antitumor effects.

Abstract Osteoarthritis, a chronic degenerative cartilage disease, is the leading cause of movement disorders among humans. Although the specific pathogenesis and associated mechanisms remain unclear, oxidative stress‐induced metabolic imbalance in chondrocytes plays a crucial role in the occurrence and development of osteoarthritis. In this study, a trimanganese tetroxide (Mn3O4) nanozyme with superoxide dismutase (SOD)‐like and catalase (CAT)‐like activities is designed to reduce oxidative stress‐induced damage and its therapeutic effect is investigated. In vitro, Mn3O4 nanozymes are confirmed to reprogram both the imbalance of metabolism in chondrocytes and the uncontrolled inflammatory response stimulated by hydrogen peroxide. In vivo, a cross‐linked chondroitin sulfate (CS) hydrogel is designed as a substrate for Mn3O4 nanozymes to treat osteoarthritis in mouse models. As a result, even in the early stage of OA (4 weeks), the therapeutic effect of the Mn3O4@CS hydrogel is observed in both cartilage metabolism and inflammation. Moreover, the Mn3O4@CS hydrogel maintained its therapeutic effects for at least 7 days, thus revealing a broad scope for future clinical applications. In conclusion, these results suggest that the Mn3O4@CS hydrogel is a potentially effective therapeutic treatment for osteoarthritis, and a novel therapeutic strategy for osteoarthritis based on nanozymes is proposed.

Abstract The unbalanced allocation of healthcare resources is a major challenge that hinders access to healthcare. Taking Shenzhen as an example, this study aimed to enhance equity in obtaining healthcare services, through measuring and visualizing the spatial accessibility of community healthcare centers (CHC), and optimizing CHC geospatial allocation. We used the number of health technicians per 10,000 to represent the CHC's service capacity, combined with resident points and census data to calculate the population the CHC needs to carry, and then analyzed the accessibility based on the Gaussian two‐step floating catchment area method. In 2020, five regions in Shenzhen had better spatial accessibility scores: Nanshan (0.250), Luohu (0.246), Futian (0.244), Dapeng (0.226), and Yantian (0.196). The spatial accessibility of CHCs shows a gradual decrease from the city center to the edge, which is affected by economic and topographic factors. With the support of the maximal covering location problem model, we selected up to 567 candidate locations for the new CHC, which could improve Shenzhen's accessibility score from 0.189 to 0.361 and increase the coverage population by 63.46% within a 15‐min impedance. By introducing spatial techniques and maps, this study provides (a) new evidence for promoting equitable access to primary healthcare services in Shenzhen and (b) a foundation for improving the accessibility of public service facilities in other areas.

BackgroundChina is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time. ObjectiveThis study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020. MethodsWe extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen’s methods to investigate the diseases’ temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality. ResultsBetween January 2005 and December 2020, 51,028,733 incident cases and 261,851 attributable deaths were recorded. Pertussis (P=.03), dengue fever (P=.01), brucellosis (P=.001), scarlet fever (P=.02), AIDS (P

Objective Previous research has shown an association of higher heart rate with an increased risk of atrial fibrillation (AF). However, the relationship between resting heart rate (RHR) and AF is unknown. The aim of this study was to investigate the association between RHR and AF in the general population of China.Design Prospective observational cohort study.Setting Community based.Participants A total of 46 126 individuals from the Kailuan study who participated in the first three surveys (2006/2007, 2008/2009 and 2010/2011) and were followed up at 2-year intervals were enrolled.Primary outcome measures The association between RHR and risk of incident AF was evaluated using Cox proportional hazards regression and restricted cubic spline models.Results Two hundred and forty-one individuals (0.52%) developed AF during 7.5 years of follow-up. After adjustment for age, sex, low-density and high-density lipoprotein, physical activity, alcohol consumption, smoking status, body mass index, mean systolic blood pressure, and history of diabetes and hypertension, the HRs were 2.32 (95% CI 1.45 to 3.72) for an RHR

BackgroundThe emergence of the new WHO classification standard in 2021 incorporated molecular characteristics into the diagnosis system for meningiomas, making the diagnosis and treatment of meningiomas enter the molecular era.Recent findingsAt present, there are still some problems in the clinical molecular detection of meningioma, such as low attention, excessive detection, and a long cycle. In order to solve these clinical problems, we realized the intraoperative molecular diagnosis of meningioma by combining real-time fluorescence PCR and AIGS, which is also the first known product applied to the intraoperative molecular diagnosis of meningioma.Implications for practiceWe applied AIGS to detect and track a patient with TERTp mutant meningioma, summarized the process of intraoperative molecular diagnosis, and expounded the significance of intraoperative molecular diagnosis under the new classification standard, hoping to optimize the clinical decision-making of meningioma through the diagnosis and treatment plan of this case.

Abstract Background Although obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study. Methods A total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk. Results During a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31–2.30) and 1.38 (95% CI: 1.11–1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF. Conclusions Elevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.

Abstract Clear evidence shows that tumors could secrete microRNAs (miRNAs) via exosomes to modulate the tumor microenvironment (TME). However, the mechanisms sorting specific miRNAs into exosomes are still unclear. In order to study the biological function and characterization of exosomal miRNAs, we performed whole-transcriptome sequencing in 59 patients’ whole-course cerebrospinal fluid (CSF) small extracellular vesicles (sEV) and matched glioma tissue samples. The results demonstrate that miRNAs could be divided into exosome-enriched miRNAs (ExomiRNAs) and intracellular-retained miRNAs (CLmiRNAs), and exosome-enriched miRNAs generally play a dual role. Among them, miR-1298-5p was enriched in CSF exosomes and suppressed glioma progression in vitro and vivo experiments. Interestingly, exosomal miR-1298-5p could promote the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) to facilitate glioma. Therefore, we found miR-1298-5p had different effects on glioma cells and MDSCs. Mechanically, downstream signaling pathway analyses showed that miR-1298-5p plays distinct roles in glioma cells and MDSCs via targeting SETD7 and MSH2, respectively. Moreover, reverse verification was performed on the intracellular-retained miRNA miR-9-5p. Thus, we confirmed that tumor-suppressive miRNAs in glioma cells could be eliminated through exosomes and target tumor-associated immune cells to induce tumor-promoting phenotypes. Glioma could get double benefit from it. These findings uncover the mechanisms that glioma selectively sorts miRNAs into exosomes and modulates tumor immunity.

In a layer house, the CO2 (carbon dioxide) concentration above the upper limit can cause the oxygen concentration to be below the lower limit suitable for poultry. This leads to chronic CO2 poisoning in layers, which manifests as listlessness, reduced appetite, weak constitution, decreased production performance, and weakened resistance to disease. Regulating ventilation may ensure a suitable CO2 concentration in layer houses. Predicting the changes in CO2 concentration and regulating the CO2 concentration in advance are key to ensuring healthy large-scale breeding of layers. In recent years, machine learning and deep learning methods have been increasingly applied to this field. A CO2 prediction model for layer house is proposed based on a GRU (gated recurrent unit) and LSTM (long short-term memory). The temperature, humidity, and CO2 were determined as inputs to the model by the correlation coefficient. The datasets of the experimental layer house were continuously measured during June–July 2023, using a self-developed environmental monitor, and the monitored data were used as samples for model inputs. There were 22,000 time series data in the datasets. In this study, multivariate time series data were standardized via data pre-processing to improve model training. GRU and LSTM models were constructed. The models were trained using a training set. Then, these trained models were used to provide predictions on a test set. The prediction errors were calculated using the true values of the test set and the predicted values provided by the models. To test the performance of the model and accuracy of the predictions, predictions were made for different numbers of datasets. The results demonstrated that the combined prediction model had good generalization, stability, and convergence with high prediction accuracy. Due to the structure of the model, the stability of the LSTM model was higher than that of the GRU model, and its prediction accuracy and speed were lower than those of the GRU model. When the datasets of the GRU model were 15,000 to 17,000, The MAE of the GRU was 70.8077 to 126.7029 ppm, and the prediction time of the GRU is 16 to 24 ms. When the LSTM model’s datasets were 15,000–20,000, the MAE of LSTM was 78.8596 to 136.0896 ppm, and the prediction time of the GRU was 17 to 26 ms.

As one of the most common post-transcriptional modifications of mRNAs and noncoding RNAs, N6-methyladenosine (m6A) modification regulates almost every aspect of RNA metabolism. Evidence indicates that dysregulation of m6A modification and associated proteins contributes to glioblastoma (GBM) progression. However, the function of fat mass and obesity-associated protein (FTO), an m6A demethylase, has not been systematically and comprehensively explored in GBM. Here, we found that decreased FTO expression in clinical specimens correlated with higher glioma grades and poorer clinical outcomes. Functionally, FTO inhibited growth and invasion in GBM cells in vitro and in vivo. Mechanistically, FTO regulated the m6A modification of primary microRNA-10a (pri-miR-10a), which could be recognized by reader HNRNPA2B1, recruiting the microRNA microprocessor complex protein DGCR8 and mediating pri-miR-10a processing. Furthermore, the transcriptional activity of FTO was inhibited by the transcription factor SPI1, which could be specifically disrupted by the SPI1 inhibitor DB2313. Treatment with this inhibitor restored endogenous FTO expression and decreased GBM tumor burden, suggesting that FTO may serve as a novel prognostic indicator and therapeutic molecular target of GBM.

Timely detection and maintenance of smart electricity meter faults are essential for smart grid systems, but there is no high-accurate algorithm to detect the meter fault yet. So, in this paper, we propose a deep learning algorithm to detect the fault of the smart electricity meter. Our algorithm is based on a 1D convolution twin network, which can distinguish the meter data of different fault types with high precision. To realize the fault detection task, we design a twin classifier for counting the number of matches between the data to be predicted and each type of known data and select the type with the most counts as the predicted type. Our algorithm automatically detects the fault of the smart electricity meter while its accuracy reaches 94.52%, which can significantly improve the maintenance efficiency of the fault detection.