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Abstract Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.

Abstract Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

Abstract Epileptogenesis is the process whereby the previously normally functioning brain begins to generate spontaneous, unprovoked seizures. Status epilepticus (SE), which entails a massive release of neuronal glutamate and other neuroactive substances, is one of the best-known triggers of epileptogenesis. We here asked whether pharmacologically promoting glymphatic clearance during or after SE is beneficial and able to attenuate the subsequent epileptogenesis. We induced SE in adult male mice by intrahippocampal kainic acid (KA) infusion. Acute administration of a cocktail of adrenergic receptor antagonists (propranolol, prazosin, and atipamezole: PPA), enhanced glymphatic flow and effectively reduced the severity of spontaneous seizures in the chronic phase. The PPA treatment also reduced reactive gliosis and inhibited the loss of polarized expression of AQP4 water channels in the vascular endfeet of astrocytes. Administration of PPA after cessation of SE (30 hours post KA) also effectively suppressed epileptogenesis and improved outcome. Conversely, mice with constitutively low glymphatic transport due to genetic deletion of the aquaporin 4 (AQP4) water channel showed exacerbation of KA-induced epileptogenesis. We conclude that the pharmacological modulation of glymphatic fluid transport may represent a potential strategy to dampen epileptogenesis and the occurrence of spontaneous seizures following KA-induced SE.

Abstract To assess the circulating characteristics of common respiratory pathogens following the complete relaxation of non-pharmaceutical interventions (NPIs) and the cessation of the dynamic zero-COVID policy. The retrospective analysis was conducted from 14,412 patients with acute respiratory infections (ARIs) from January 24, 2020, to December 31, 2023, including Influenza A virus (IFV-A), Influenza B virus (IFV-B), Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV), Human Parainfluenza Virus (HPIV), Human Metapneumovirus (HMPV), Human Coronavirus (HCoV), Human Bocavirus (HBoV), Human Adenovirus (HAdV), and Mycoplasma pneumoniae (MP). Compared with 2020–2022, Joinpoint analysis indicated a monthly increase in overall pathogen activity in 2023, rising from an average of 43.05% to an average of 68.46%. The positive rates of IFV-A, IFV-B, HMPV, HPIV, HCoV, and MP increased, while those of HRV and RSV decreased, and no differences in HAdV and HBoV. The outbreak of IFV-A and MP was observed, the positive rate of MP has surpassed pre-COVID-19 pandemic levels and the spread of RSV was interrupted by IFV-A. Infants and toddlers were primarily infected by HRV and RSV, Children and adolescents exhibited a higher prevalence of infections with MP, IFV-A, and HRV, whereas Adults and the elderly were primarily infected by IFV-A. The incidence of co-infections rose from 4.25 to 13.73%. Restricted cubic spline models showed that the susceptible age ranges for multiple pathogens expanded. These changes serve as a reminder to stay alert in the future and offer clinicians a useful guide for diagnosing and treating.

Abstract Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4+C1q+ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies. Novelty & Impact Statements We identified a group of macrophages (FABP4+C1q+ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4+C1q+ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.

This research evaluated cow dung compost (CDC), goose dung compost (GDC), and duck dung compost (DDC) as peat addition in growing media used for the production of pumpkin seedlings. Commercial substrate (peat: vermiculite: perlite=3:1:1, v/v) was used as the control (CK). The partial addition in peat of each waste compost in the mixtures were 10%, 20%, and 30% (v/v). The results showed that all compost in mixtures increased bulk density, total porosity, electrical conductivity, and mineral content, but negatively affected the pH and organic matter of the growing media compared to CK. CDC in mixture increased ventilation porosity and gas-water ratio and decreased water-holding porosity compared to CK, which was the opposite of the effect of GDC and DDC. The mixtures elaborated with GDC showed better growth, biomass, gas exchange parameters, and physiological indicators of seedling plants than other treatments in varying degrees, which depended on the additional amount of GDC. DDC inhibited plant growth and gas exchange parameters, especially in high addition rate; however, it had a slight promotion effect on chlorophyll content and quality because DDC was rich in minerals. GDC was better than CDC and DDC as a partial addition for peat in the cultivation of pumpkin seedlings.

Background: The brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. Objectives: To explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. Methods: Female Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. Results: Perinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T3) levels, and both were linked to neurobehavioral disorders. Conclusion: Exposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T3 homeostasis.

Abstract We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient’s ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers.

Abstract Background This study was designed to compare the diagnostic efficacy of mSEPT9 to four blood markers (CEA, CA19-9, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR)). In addition, we aimed to determine the combined diagnostic efficacy of mSEPT9, CEA, CA19-9, PLR and NLR in colorectal cancer. Methods A total of 567 participants were enrolled in the study, including 308 CRC patients, 61 colorectal polyp patients and 198 healthy subjects confirmed by colonoscopy and/or tissue biopsy. Plasma samples were collected for tests. Results The positive rate of mSEPT9 in CRC (71.8%) was markedly higher than that in either the colorectal polyps group (27.9%) or the healthy controls (6.1%) (P

Abstract Background Acute ischemic stroke (AIS) is a major global public health issue. There is limited research on the relationship between ambient temperature and AIS hospital admissions, and the results are controversial. Our objective is to assess the short-term impact of ambient temperature on the risk of AIS hospital admissions in Yancheng, China. Methods We collected data on daily AIS hospital admissions, meteorological factors, and air quality in Yancheng from 2014 to 2019. We used Poisson regression to fit generalized linear models and distributed lag non-linear models to explore the association between ambient temperature and AIS hospital admissions. The effects of these associations were evaluated by stratified analysis by sex and age. Results From 2014 to 2019, we identified a total of 13,391 AIS hospital admissions. We observed that the influence of extreme cold and heat on admissions for AIS manifests immediately on the day of exposure and continues for a duration of 3–5 days. Compared to the optimal temperature (24.4 °C), the cumulative relative risk under extreme cold temperature (-1.3 °C) conditions with a lag of 0–5 days was 1.88 (95%CI: 1.28, 2.78), and under extreme heat temperature (30.5 °C) conditions with a lag of 0–5 days was 1.48 (95%CI: 1.26, 1.73). Conclusions There is a non-linear association between ambient temperature and AIS hospital admission risk in Yancheng, China. Women and older patients are more vulnerable to non-optimal temperatures. Our findings may reveal the potential impact of climate change on the risk of AIS hospital admissions.

Abstract Background The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. Methods A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. Results Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. Conclusions Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF. Graphical abstract

This paper is based on panel data from 278 prefecture-level cities in China from 2012 to 2021, and studies the relationship between healthy real estate development, land finance, and economic growth. The findings indicate that there are distinct trends in the healthy development of real estate across different city levels in China. By using the PVAR model, the intrinsic connections between real estate health, industrial transformation and upgrading, and economic growth are revealed. The results from the heterogeneity analysis show that the lag periods of real estate health, land finance, and economic growth have a positive impact on themselves in municipalities, provincial capitals, and prefecture-level cities. In prefecture-level cities, there is a significant interactive promotion between healthy real estate development and land finance. Land finance can directly contribute to economic growth, forming a “land finance-economic growth” direct effect channel. Additionally, healthy real estate development has a significant positive impact on promoting economic growth.

Summary: The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP+) and neuron-derived neurotrophic factor-expressing (NDNF+) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV+) or somatostatin-expressing (SOM+) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG.

IntroductionEarly and accurate diagnosis of tuberculosis (TB) is crucial for initiating timely treatment and preventing new infections. In this study, we introduced the iFIND TBR assay, an automated all-in-one tuberculosis detection approach that simultaneously detect Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance.MethodsThe limits of detection (LOD), sensitivity, specificity, and RIF-R rpoB mutation detection of the iFIND TBR were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M.tuberculosis H37Rv. Frozen clinical samples from patients suspected of having TB were also tested.ResultsThe LOD of the iFIND TBR for MTB detection were 13.34 CFU/ml (95% CI, 11.71-16.47), and for RIF resistance was 109.79CFU/mL (95% CI, 95-138.19). The iFIND TBR assay accurately distinguish MTB strains from non-tuberculous mycobacteria (NTM) without any cross reactivity. Testing on 157 clinical sputum samples, compared with the bacteriologically TB standard, the overall sensitivity and specificity of the iFIND TBR was 100% (95%CI, 94.64, 100) and 85.29% (95% CI, 74.61, 92.72), respectively. When assessing RIF susceptibility, the iFIND TBR achieved a sensitivity of 98.15% (95% CI, 90.11–99.95) and a specificity of 85.71% (95% CI, 67.33–95.97), compared with phenotypic drug susceptibility testing. Discordant RIF susceptibility results were more frequently observed in samples exhibiting heteroresistance.DiscussionThese findings demonstrate that iFIND TBR assay performs well in detecting TB and RIF resistance, and shows promise as a point-of-care tool in resource-limited areas.

AimsThe objective of this study was to investigate the associations of dietary and circulating antioxidant vitamins with metabolic syndrome (MetS), and to assess causality using Mendelian randomization (MR).MethodsThis study included 10,308 participants from the National Health and Nutrition Examination Survey. The associations of vitamins A, C, E and carotenoids with MetS were assessed using multivariable weighted logistic regression analysis. Subsequently, the MR approach was employed to test the causal associations, with inverse variance weighted (IVW) serving as the primary analysis.ResultsObservationally, dietary vitamin A (OR=0.852, 95%CI: 0.727-0.999), C (OR=0.802, 95%CI: 0.675-0.952), carotene (OR=0.832, 95%CI: 0.706-0.982), and β-carotene (OR=0.838, 95%CI: 0.706-0.995) in quartile 4 had lower incidents of MetS, when compared to quartile 1. Circulating vitamin C and carotene were also present inversely associated with MetS, while the vitamin A and E both increased this risk. IVW-MR confirmed the associations of dietary vitamin A (OR=0.920, 95%CI: 0.861-0.984), vitamin C (OR=0.905, 95%CI: 0.836-0.979) and carotene (OR=0.918, 95%CI: 0.865-0.974) with MetS. However, there was only circulating β-carotene (OR=0.909, 95%CI: 0.857-0.965) was found to be causally associated with MetS.ConclusionsObservational and MR studies have shown that adequate dietary intake of vitamin A, C and carotenoids may help to reduce the risk of MetS.

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment.STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.

ObjectiveThe exposure of the content posted by doctors on social media has the potential to influence how patients perceive and judge doctors. It is necessary to further investigate whether and how the content posted by doctors affects patients’ health behaviors and outcomes, as well as to identify the factors that may influence this mechanism.MethodsMulti-respondent survey data was collected from 35 doctors and 322 patients in China, and structural equation modeling (SEM) was used to test the hypothesis model.ResultsThe findings revealed that doctors posting professional knowledge content on social media positively impacted patient adherence and treatment effectiveness. Conversely, doctors sharing personal life-related content on social media were associated with lower patient adherence and poorer treatment outcome. Moreover, doctor gender and doctor humor moderate the relationship between social media behavior of doctors and patient adherence.ConclusionDoctors sharing professional knowledge on social media not only fosters trust in physicians but also closely correlates with patient adherence and treatment effectiveness.

The widespread occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) in aquatic environments and its hazards to aquatic species underscore the necessity of comprehending its environmental fate. Here, we investigated the transformation from 6PPD to 6PPD-Q and the attenuation of 6PPD-Q in surface water under natural conditions. Contrary to prior findings, this work revealed that 6PPD-Q and its precursor 6PPD-OH/6PPD-(OH)2, were not detected through target analysis and suspect screening during 6PPD transformation in the surface water under the natural conditions. 6PPD-Q predominantly accumulated in TWPs in ambient atmosphere with 1.28 % mass yield from the 6PPD dissipation. Subsequently, 6PPD-Q was eluted from TWPs and released to the water environment. The investigation on the natural attenuation of 6PPD-Q in the surface water demonstrated that direct and indirect photolysis facilitated the rapid dissipation of 6PPD-Q with a half-life of 2.57 h. Utilizing the liquid chromatography high resolution mass spectrometry (LC-HRMS), including both time of flight (TOF) MS and Orbitrap MS, twelve novel transformation products (TPs) of 6PPD-Q were identified by using a comprehensive non-targeted screening strategy. The results from two dimensions gas chromatography (GC×GC) TOF-MS revealed additional two TPs. Based on the molecular structure of TPs, four major pathways of 6PPD-Q attenuation were proposed, including bond cleavage, hydroxylation, quinone cleavage and rearrangement. All TPs were predicted to exhibit lower toxicity, indicating the natural attenuation of 6PPD-Q reduced its toxicity and potential environmental risks. This study provides crucial insights into the environmental fate of 6PPD-Q, highlighting the significance of understanding both its formation from 6PPD and its subsequent attenuation processes under natural conditions.

BackgroundLeisure activities serve as key measures to enhance the subjective happiness of middle-aged and older adults individuals and to positively address the challenges of an aging society; however, the trajectory of changes in their participation in leisure activities and how these changes relate to shifts in subjective happiness have not been adequately explored.MethodsThis study selected data from the China Health and Aging Longitudinal Study (CHARLS), which included a total of 5,190 middle-aged and older adults people. Linear and nonlinear latent growth models, parallel latent growth models and cross-lagged models were constructed to investigate the influence and lagged relationship between the trajectory of changes in the level of participation in leisure activities on the trajectory of changes in the subjective well-being of middle-aged and older adults people.ResultsThe initial level of physical activity participation of middle-aged and older adults people significantly predicted the initial level (β = 1. 203, p

BackgroundWheat germ is known for its antioxidant, anti-inflammatory, and disease resistance properties in animals. However, its effect on the gut of Sichuan white geese remains unclear.MethodIn this study, thirty 250-day-old geese were divided into three equal groups, the control group, LWG group (21.8% wheat germ) and HWG group (43.6% wheat germ), the experiment lasted 12 weeks. We assessed various aspects of geese intestinal health, including barrier function, digestibility, antioxidant capacity, immunity, microbiota, and metabolism.ResultsThe study revealed a significant increase in villus height (VH), villus height-to-crypt depth (VH/CD) ratio, amylase, and lipase activities in the duodenum and ileum, increased putrescine levels in the duodenum and jejunum, as well as spermidine levels in the jejunum (P < 0.05). LWG increased the total antioxidant capacity (T-AOC) in the duodenum, while decreasing levels of intestinal malondialdehyde (MDA), serum lipopolysaccharide (LPS), interleukin-6 (IL-6), and diamine oxidase (DAO) activity (P < 0.05). Furthermore, LWG increased the relative abundance of Oscillospiraceae_unclassified, Ligilactobacillus, and Roseburia, as well as increased levels of acetic acid, butyric acid, and valeric acid, while decreasing the relative abundance of Subdoligranulum, Flavonifractor, and Klebsiella. Additionally, we observed 17 up-regulated genes and 25 down-regulated genes in the jejunum, which are associated with the cell cycle and immunity. These genes play roles in pathways such as the p53 signaling pathway, cell cycle regulation, and pathways associated with immune modulation. On the other hand, HWG increased intestinal VH and spermidine levels, as well as amylase and lipase activities in the duodenum (P < 0.05). It also elevated ileal T-AOC and sIgA levels (P < 0.05), while reducing intestinal MDA content, serum LPS levels, DAO activity, and propionic acid in cecum contents (P < 0.05). Moreover, HWG increased the relative abundance of Ligilactobacillus, Oscillospiraceae_unclassified, and Roseburia (P < 0.05).ConclusionOverall, wheat germ diets, particularly the LWG diet demonstrated the ability to enhance antioxidant capacity, digestibility, immunity, and barrier properties of the intestinal tract, while modulating the gut microbiota and metabolism. Therefore, wheat germ diets hold promise in improving intestinal health by preserving barrier function and regulating flora structure.

China has abundant straw resources, but challenges in utilization persist. Utilization rates need improvement, and environmental pollution from straw burning remains a significant issue. Accurate and intelligent remote sensing classification of straw types is crucial for enhancing straw utilization and preventing straw burning. This paper proposed a new approach for the intelligent classification of maize straw types, using the DenseNet201 deep transfer learning algorithm based on RGB images captured by Unmanned Aerial Vehicle (UAV). The sample labels dataset was established for maize straw types, utilizing DenseNet201 deep transfer learning algorithm to pre-train the sample set. This pre-training facilitated model transfer and parameter initialization. Subsequently, the second round of deep transfer learning was performed to construct the final maize straw type remote sensing classification models using DenseNet201 deep transfer learning algorithm. This model and results were subsequently compared with maize straw type classification by the ResNet50 and GoogLeNet deep transfer learning algorithms, as well as maize straw type classification using DenseNet201, ResNet50, and GoogLeNet deep learning algorithms. The results showed that the accuracy of the pre-trained maize straw type deep transfer learning remote sensing classification model surpassed that of the untrained maize straw type deep learning remote sensing classification model, resulting in an enhancement of accuracy by 8.59%, 7.38%, and 1.28%, respectively. The DenseNet201 deep transfer learning model for maize straw types exhibited the highest accuracy with the overall accuracy of 95.57%, and the kappa coefficient of 0.9410. Hence, the DenseNet201 deep transfer learning classification of maize straw types enabled the attainment of intelligent remote sensing recognition of maize straw types. The classification methodology, model, and results presented in this paper can serve as valuable technical references, offering essential information support for agricultural and environmental protection departments actively involved in the comprehensive utilization of straw resources and atmospheric environmental protection efforts.

Abstract Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4’s function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

In this paper, we studied a Hadamard-type fractional Riemann-Stieltjes integral boundary value problem. The existence of nontrivial solutions was obtained by using the fixed-point method when the nonlinearities can be superlinear, suberlinear, and have asymptotic linear growth. Our results improved and generalized some results of the existing literature.

In this work, we investigate a Riemann-Liouville-type impulsive fractional integral boundary value problem. Using the fixed point index, we obtain two existence theorems on positive solutions under some conditions concerning the spectral radius of the relevant linear operator. Our method improves and generalizes some results in the literature.

Cellular traction forces (CTFs) are generated by adherent cells and involved in regulating migration, morphology, and homeostasis. Accurate measurement of CTFs is crucial for understanding fundamental biological processes such as morphogenesis, angiogenesis, and wound healing. However, directly measuring CTFs, which typically range in the nanonewton scale, is challenging. Cellular traction force microscopy (TFM) has been developed to quantify CTFs, but detailed operational procedures and complex data analysis limit its applicability. In this study, hydrogels embedded with fluo-spheres serve as the substrate for TFM measurement under a detailed TFM protocol. Additionally, we designed a user-friendly program for easy parameter setting. An open-source program called Python Fourier transform traction cytometry (pyFTTC) is introduced for data analysis, utilizing particle image velocimetry (PIV) to calculate the traction force from a batch of images. Cross-correlation based PIV and L2-regularized FTTC are applied to all images for data analysis. This article provides a straightforward protocol for quantifying CTFs in standard laboratories, facilitating both cell biology studies and biomaterials development.

The Yellow River is the main source of water for urban and rural area and agricultural irrigation in northern China. Herein, the distribution and risk assessment of perfluoroalkyl acids (PFAAs) were investigated from the Yellow River in Shandong Province, China. The total concentration of PFAAs (∑PFAAs) in surface water and sediments were 37.5–2128 ng/L (mean: 167 ng/L) and not detected−6.95 ng/g dry weight (dw) (mean: 1.02 ng/g dw), respectively. Short-chain PFAAs-perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulfonic acid (PFBS) were the most prevalent PFAAs in surface water. Source analysis showed that firefighting foam (proportion: 31.3 %) and textile treatments and food packaging (proportion: 30.3 %) were the main sources of PFAAs in water. Based on the concentration of PFAAs in water, ecological and potential human health risks were assessed. Perfluorooctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA) and perfluoroundecanoic acid (PFUnDA) posed nonnegligible ecological risk for some aquatic organisms. Levels of PFAAs (e.g., PFOA, PFNA, and PFDA etc.) in some water samples were higher than the advisory guidelines of PFAAs concentrations in water worldwide, indicating a potential human health risk. Therefore, PFOA, PFNA, PFDA, and PFUnDA are the key focus of pollutants in the water of the Yellow River in Shandong Province, and the standards and limits of these PFAAs in environments including surface water and sediment should be promoted.

ABSTRACTGBM is one of the most malignant tumor in central nervous system. The resistance to temozolomide (TMZ) is inevitable in GBM and the characterization of TMZ resistance seriously hinders clinical treatment. It is worthwhile exploring the underlying mechanism of aggressive invasion and TMZ resistance in GBM treatment. Bioinformatic analysis was used to analyze the association between RND1 and a series of EMT-related genes. Colony formation assay and cell viability assay were used to assess the growth of U87 and U251 cells. The cell invasion status was evaluated based on transwell and wound-healing assays. Western blot was used to detect the protein expression in GBM cells. Treatment targeted RND1 combined with TMZ therapy was conducted in nude mice to evaluate the potential application of RND1 as a clinical target for GBM. The overexpression of RND1 suppressed the progression and migration of U87 and U251 cells. RND1 knockdown facilitated the growth and invasion of GBM cells. RND1 regulated the EMT of GBM cells via inhibiting the phosphorylation of AKT and GSK3-β. The promoted effects of RND1 on TMZ sensitivity was identified both in vitro and in vivo. This research demonstrated that the overexpression of RND1 suppressed the migration and EMT status by downregulating AKT/GSK3-β pathway in GBM. RND1 enhanced the TMZ sensitivity of GBM cells both in vitro and in vivo. Our findings may contribute to the targeted therapy for GBM and the understanding of mechanisms of TMZ resistance in GBM.

Natural environments play a crucial role in transmission of antimicrobial resistance (AMR). Development of methods to manage antibiotic resistance genes (ARGs) in natural environments are usually limited to the laboratory or field scale, partially due to the complex dynamics of transmission between different environmental compartments. Here, we conducted a nine-year longitudinal profiling of ARGs at a watershed scale, and provide evidence that restrictions on livestock farms near water bodies significantly reduced riverine ARG abundance. Substantial reductions were revealed in the relative abundance of genes conferring resistance to aminoglycosides (42%), MLSB (36%), multidrug (55%), tetracyclines (53%), and other gene categories (59%). Additionally, improvements in water quality were observed, with distinct changes in concentrations of dissolved reactive phosphorus, ammonium, nitrite, pH, and dissolved oxygen. Antibiotic residues and other pharmaceuticals and personal care products (PPCPs) maintain at a similarly low level. Microbial source tracking demonstrates a significant decrease in swine fecal indicators, while human fecal pollution remains unchanged. These results suggest that the reduction in ARGs was due to a substantial reduction in input of antibiotic resistant bacteria and genes from animal excreta. Our findings highlight the watershed as a living laboratory for understanding the dynamics of AMR, and for evaluating the efficacy of environmental regulations, with implications for reducing environmental risks associated with AMR on a global scale.

BackgroundSince the outbreak of COVID-19, China has implemented a series of non-pharmaceutical interventions (NPIs), effectively containing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as various respiratory pathogens. With the continuous relaxation of restrictions, China has entered a new phase of the post-pandemic era. However, the epidemiological differences of Mycoplasma pneumoniae (MP) between the two phases in Ningbo and even in China remain unclear.MethodsData of children aged 0–14 years who visited the Ningbo Medical Center LiHuiLi Hospital due to acute respiratory tract infections from January 2020 to December 2023 were collected. PCR was used to detect 13 respiratory pathogens and the macrolide-resistance of Mycoplasma pneumoniae.ResultsAmong 10,206 children, 2,360 were infected with MP (23.12%). Among the total, the MP positive rate during the NPI phase (6.35%) was significantly lower than that during the non-NPI phase (34.28%), while the macrolide resistance rate increased from 62.5% (NPI phase) to 81.1% (non-NPI phase). The rate of MP co-infection increased from 11.2% (NPI phase) to 30.3% (non-NPI phase). MP infection exhibited obvious seasonality, with the highest prevalence in autumn (30.0%) followed by summer (23.6%). There were differences in MP positivity rates among different age groups, with the highest among school-age children at 39.5%. During the NPI phase, all age groups were less susceptible to MP, while during the non-NPI phase, the susceptible age for MP was 4–12 years, with 8 years being the most susceptible. The susceptible age for MP co-infection was 0–6 years. MP exhibited antagonistic effects against numerous pathogens. Compared to MP single infection, the proportion of pneumonia was higher in MP co-infection cases.ConclusionThe removal of NPIs significantly impacted the spread of MP, altering population characteristics including age, seasonality, macrolide resistance, and MP co-infection rates.

BackgroundPostoperative delirium (POD) is a common anesthetic side effect in cardiac surgery. However, the role of oxygen saturation monitoring in reducing postoperative delirium has been controversial. Therefore, this meta-analysis aimed to analyze whether NIRS monitoring during cardiac surgery under cardiopulmonary bypass could reduce the incidence of postoperative delirium.MethodsPubMed, Web of Science, Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) databases were systematically searched using the related keywords for randomized-controlled trials (RCTs) published from their inception to March 16, 2024. This review was conducted by the Preferred Reporting Project and Meta-Analysis Statement (PRISMA) guidelines for systematic review. The primary outcome was postoperative delirium, and the second outcomes included the length of ICU stay, the incidence of kidney-related adverse outcomes, and the incidence of cardiac-related adverse outcomes.ResultsThe incidence of postoperative delirium could be reduced under the guidance of near-infrared spectroscopy monitoring (OR, 0.657; 95% CI, 0.447–0.965; P = 0.032; I2 = 0%). However, there were no significant differences in the length of ICU stay (SMD, 0.005 days; 95% CI, −0.135–0.146; P = 0.940; I2 = 39.3%), the incidence of kidney-related adverse outcomes (OR, 0.761; 95% CI, 0.386–1.500; P = 0.430; I2 = 0%), and the incidence of the cardiac-related adverse outcomes (OR, 1.165; 95% CI, 0.556–2.442; P = 0.686; I2 = 0%) between the two groups.ConclusionNear-infrared spectroscopy monitoring in cardiac surgery with cardiopulmonary bypass helps reduce postoperative delirium in patients.Systematic Review RegistrationPROSPERO, identifier, CRD42023482675

Abstract Purpose Lung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM. Methods We retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively. Results The median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM. Conclusions This single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

BackgroundCuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear.MethodsMale C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment.ResultsCPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of Lactobacillus and Bifidobacterium in CPZ-treated mice.ConclusionThe anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.

Abstract Background Green tea has been reported to be potentially protective against the development of cardiovascular disease (CVD). This study aimed to investigate the association between green tea consumption and incident CVD in type 2 diabetes (T2D) patients with overweight/obesity. Methods A total of 4756 Chinese overweight/obese T2D patients were recruited and followed up for 6.27 years. Information on green tea consumption was collected at baseline using interviewer-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD according to green tea consumption were estimated using the Cox proportional hazards model. Results Compared with non-habitual consumers, participants who consumed > 5 g/day of green tea leaves reduced the risk of CVD by 29% (95%CI: 0.55–0.92), stroke by 30% (95%CI: 0.51–0.95) and coronary heart disease (CHD) by 40% (95%CI: 0.40–0.89). Similarly, participants who consumed green tea for ≥ 40 years reduced the risk of CVD by 31% (95%CI: 0.54–0.88), stroke by 33% (95%CI: 0.50–0.90) and CHD by 39% (95%CI: 0.42–0.88). Among participants with 5 g/day of tea leaves and > 40 years of tea consumption were associated with 59% (95%CI: 0.23–0.72) and 57% (95%CI: 0.26–0.74) reduced risk of stroke, respectively. However, among participants with ≥ 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with a 50% (95%CI: 0.30–0.82) and 46% (95%CI: 0.35–0.85) reduced risk of CHD, respectively. Conclusions Green tea consumption is associated with reduced risk of CVD, stroke, and CHD in overweight/obese T2D patients.

Abstract Background Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice. Methods An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro. Results Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-α) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG. Conclusions AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model.

As the reform of electricity marketization advances, the virtual power plant (VPP), as an emerging market participant, is being progressively incorporated into the trading scope of both the electricity spot market (ESM) and the reserve market (RM). Due to its flexible regulation capabilities, the bidding strategies of VPPs in the electricity market are complex and variable, presenting new challenges to the joint operation of power markets. In this context, first, based on the interactive game relationships among multiple market entities under the operating mechanisms of the spot and reserve markets, this paper designs a principal-follower game framework for transactions in these markets with the VPP as the main entity. Second, it constructs a two-level joint optimized bidding strategy model for VPP participation in the spot and reserve markets, where the inner layer is the VPP’s optimized bidding strategy model aiming to maximize the total revenue from the spot and reserve markets; the outer layer is the spot and reserve market clearing model targeting the minimization of the total electricity purchasing cost for society. Finally, the simulation case analysis shows that the proposed method can achieve joint optimal operation of the electricity spot and reserve markets by considering the VPP bidding strategy, resulting in a 1.42% reduction in the total electricity purchase cost of the power market.

Most of the existing superpixel segmentation-based synthetic aperture radar (SAR) target detection algorithms cannot keep the independence of small targets under complex background, especially when the size of the targets varies greatly. Focusing on the problem, we propose a novel local fuzzy iterative superpixel segmentation method using edge information (LFI-EI) for SAR image target detection. First, we use an edge detector to extract the edge information in the SAR image. Second, a new superpixel initialization method combining the edge information is proposed and a dissimilarity measurement is defined. Third, instead of hard iterative clustering, we introduce the fuzzy theory to construct local fuzzy iterative clustering to obtain the superpixel segmentation result. Finally, a small regions integration step using edge information is implemented to enhance the superpixel segmentation result. By comparing the superpixel segmentation results of three competitors on simulated SAR images and real SAR images, it can be found that the proposed LFI-EI method can achieve satisfying superpixel segmentation performance, and the problem that small targets cannot maintain their independence when the size of targets varies greatly in the SAR image can be solved to some extent. Meanwhile, based on the LFI-EI superpixel segmentation method, the LFI-EI detector is proposed for target detection. The detector uses the contrast features between superpixels to transform the detection problem into a classification problem, and ultimately obtains the target detection result. The target detection experiment on the superpixel segmentation results proves that LFI-EI detector has good detection performance, and further verifies the superiority of the proposed LFI-EI superpixel segmentation method.

High-Al-content n-AlGaN ohmic contact is very important for deep ultraviolet optoelectrical devices. However, it often suffers from the etching damages formed in inductively coupled plasma (ICP) etching. In this paper, the effects of ICP etching parameters on n-Al0.5Ga0.5N ohmic contact, including RF power, ICP power, and etching gas, were systematically investigated and analyzed by X-ray photoelectron spectroscopy and circular transmission line model. Finally, n-Al0.5Ga0.5N ohmic contact was achieved with a low specific contact resistivity of 8.7×10-4 Ω·cm2, and AlGaN-based UVC light-emitting diodes (LEDs) showed a low operation voltage of only 5.6 V at the injection current density of 16 A/cm2.

In order to improve the efficiency of energy utilization, the integrated energy system (IES) has emerged. The IES typically acts as a whole system during operations, the subsystems are separated, and the interests of each system are independent. In this paper, considering the relationship between the various energy systems, non-cooperative game theory is used to establish the optimal dispatch model. The proposed model mainly relies on the relationship between the cooperation and competition among various subsystems to obtain the maximum benefit they can accept. Furthermore, the basic definition is combined with the particle swarm optimization algorithm to solve the problem. The results show that the optimization strategy proposed in this paper can operate safely and reliably, and effectively distribute the benefits of each energy system.

Abstract Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

The global repercussions of the COVID-19 pandemic on economies and public health worldwide have been profound. This study aims to examine the developmental trends of the COVID-19 pandemic, establish predictive models, and provide insights for effective control measures against potential future disease outbreaks. Considering the coexistence of both linear and nonlinear factors in COVID-19 data, conventional single-machine learning and traditional forecasting models encounter challenges in accurately predicting pandemic trends. To enhance the precision of COVID-19 pandemic predictions by integrating linear and nonlinear factors, this study proposes three combined forecasting models: CNN-LSTM-ARIMA, TCN-LSTM-ARIMA, and SSA-LSTM-ARIMA. These models leverage the strengths of deep learning in capturing nonlinear factors and the capabilities of the traditional ARIMA model in handling linear factors. Initially, LSTM and ARIMA models are used to model and predict the COVID-19 pandemic in Quebec, Canada. Subsequently, CNN models, TCN models, and the Sparrow Search Algorithm are employed to integrate predictions from the LSTM and ARIMA models. Comparative analyses of the three combined models, it was found that the CNN-LSTM-ARIMA model exhibits the highest predictive accuracy, with an MSE of 7048.26, RMSE of 83.95, MAE of 61.18, MAPE of 0.16, and $R^{2}$ of 0.95. To validate the applicability and stability of the CNN-LSTM-ARIMA model in predicting COVID-19 pandemics, Italian COVID-19 pandemic data was employed. The three combined forecasting models are established and evaluated using model evaluation metrics. The results affirm that the CNN-LSTM-ARIMA model remains the optimal choice, underscoring its high stability and suitability for COVID-19 pandemic forecasting endeavors.

The Three Gorges hydropower station in China creates a large reservoir by diverting water from the Yangtze River, increasing the risk of geological disasters, especially massive landslides along the reservoir shoreline. To mitigate these risks, improving geological monitoring and early warning systems is crucial. Interferometric Synthetic Aperture Radar (InSAR) is widely used to monitor reservoir bank landslides. However, its potential in early warning systems is limited due to temporal resolution constraints, preventing timely warnings. To address this, we propose integrating daily hydrological data (precipitation and water level observations) with historical InSAR deformation sequences using our deep learning-based multivariate united state estimation network, “MUSEnet.” This approach generates customized daily landslide deformation products for high-risk areas, greatly enhancing early warning capabilities by providing timely and accurate information on landslide occurrence and magnitude. We validated our method using 161 Sentinel-1 A images of the Xinpu landslide in the Three Gorges Reservoir area. Through statistical analysis, we identified different degrees of influence from rainfall and reservoir water level on the deformation of the Xinpu landslide at various locations. Additionally, we observed distinct lag times between deformation and corresponding rainfall and reservoir water level events. By utilizing deep learning, our method estimates nonlinear states by considering hysteresis and intelligently accounts for the impact of rainfall and reservoir water level, resulting in more accurate estimations compared to traditional models.

Abstract Background Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, $${x}^{2}$$ x 2 was obtained using the formula $${x}^{2}=$$ x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P

Sulfur dioxide (SO2) is a typical pollutant that affects human health, climate, and environmental and ecological conditions. China has been experiencing high concentrations of SO2, particularly in urban areas, since the 1990s. In 2010, a “joint prevention and control” (JPC) policy was issued to address air pollution problems and strengthen the regulation of SO2 emissions. This study aimed to describe the mitigation effects of this policy on SO2 emissions in 116 Chinese cities from 2003 to 2017. We applied global and local Moran's I indices to confirm the presence of significant spatial autocorrelation in SO2 emissions and constructed four spatial models to assess the effect of the JPC policy in reducing SO2 emissions and its transmission mechanism. We found that the policy decreased SO2 emissions by 1.89 × 104 tons, SO2 intensity by 1.70 tons per km2, and SO2 per capita of 158.49 tons per 10,000 people in each city, on average, all of which are significant changes. The empirical results also show that population growth, economic structure, and environmental protection significantly decrease SO2 emissions. Finally, we recommended policies to encourage regional cooperation under the JPC policy, with the aim of promoting further reductions in SO2 emissions.

Quantum entanglement detection is one of the fundamental tasks in quantum information science. Conventional methods for quantum state tomography exhibit limitations in scalability as the number of qubits increases, leading to exponential growth in the number of unknown parameters and required measurements. Consequently, the accuracy enhancement achieved by these methods is constrained. In response to this challenge, we developed a tailored convolutional neural network (CNN) model capable of effectively detecting entanglement in two-qubit quantum states, achieving an accuracy exceeding 97.5%. Notably, even in the presence of noise, this model retains its robust performance, displaying resilience against a tolerable level of noise contamination. Furthermore, the inherent generalization power of CNNs allows our model, which was initially trained on a specific spectrum of quantum states, to extend its applicability to wider states, positioning it as an outstanding tool for the further application of machine learning in the field of quantum computing, opening up new pathways for solving entanglement detection problems in quantum information.

Landslides are the most serious geological disaster in our country, causing economic losses. Because they go undetected, a large number of landslides that have caused disasters are not in the catalogue. At present, Interferometric Synthetic Aperture Radar (InSAR) has been widely used in the identification of landslides. However, it is time-consuming, inefficient, etc., to survey landslides throughout our large country. In the context of massive SAR data, this problem is more obvious. Therefore, based on the current technique of using differential interferogram phase gradient stacking to avoid phase unwrapping errors, a landslide phase gradient dataset has been constructed. To validate the dataset’s effectiveness and applicability, deep learning methods were introduced, applying the dataset to four networks: U-Net, Attention-Unet, Bisenet v2, and Deeplab v3. The results indicate that the phase gradient dataset performs well across different models, with the Attention-Unet network demonstrating the best performance. Specifically, the precision, recall, and accuracy on the test dataset were 0.8771, 0.8712, and 0.9834, respectively, and the accuracy on the validation dataset was 0.8523. Finally, in this paper, the model is applied to landslide identification in Gansu Province, China, during 2022-2023, and a total of 1882 landslides are found. These landslides are mainly concentrated in the south of Gansu Province, where the terrain is relatively undulating. The results show that this method can quickly and accurately realize landslide automatic identification in a wide area and provide technical support for large-scale landslide disaster surveys.

InSAR and optical techniques represent two principal approaches for the generation of large-scale Digital Elevation Models (DEMs). Due to the inherent limitations of each technology, a single data source is insufficient to produce high-quality DEM products. The increasing deployment of satellites has generated vast amounts of InSAR and optical DEM data, thereby providing opportunities to enhance the quality of final DEM products through the more effective utilization of the existing data. Previous research has established that complete DEMs generated by InSAR technology can be combined with optical DEMs to produce a fused DEM with enhanced accuracy and reduced noise. Traditional DEM fusion methods typically employ weighted averaging to compute the fusion results. Theoretically, if the weights are appropriately selected, the fusion outcome can be optimized. However, in practical scenarios, DEMs frequently lack prior information on weights, particularly precise weight data. To address this issue, this study adopts a fully connected artificial neural network for elevation fusion prediction. This approach represents an advancement over existing neural network models by integrating local elevation and terrain as input features and incorporating curvature as an additional terrain characteristic to enhance the representation of terrain features. We also investigate the impact of terrain factors and local terrain feature as training features on the fused elevation outputs. Finally, three representative study areas located in Oregon, USA, and Macao, China, were selected for empirical validation. The terrain data comprise InSAR DEM, AW3D30 DEM, and Lidar DEM. The results indicate that compared to traditional neural network methods, the proposed approach improves the Root-Mean-Squared Error (RMSE) ranges, from 5.0% to 12.3%, and the Normalized Median Absolute Deviation (NMAD) ranges, from 10.3% to 26.6%, in the test areas, thereby validating the effectiveness of the proposed method.

Flexible cages are widely used in marine aquaculture, yet their mechanical features in extreme seas are still unclear. This study proposes a numerical algorithm to solve the coupled response of the multiple cage systems. The net and mooring lines are modeled using the lumped-mass model, while the flexible floating collar system is assessed with the large-deformation FEM model, and the two models are coupled through an iterative scheme. Sea trials are conducted, and the motion of the cage is obtained using an image processing technique, which validates the numerical algorithm. Using the proposed numerical algorithm, a series of simulations are performed to investigate the response of flexible cages in extreme seas. Motions, line tensions, and structural sectional forces are studied, and the effects of factors such as the wavelength of incident waves and the diameter of collar pipes are investigated.

We attained wurtzite ScxAl1−xN (0.16 ≤ x ≤ 0.37) thin films by varying the Sc and Al fluxes at a fixed active nitrogen flux during plasma-assisted molecular beam epitaxy. Atomic fluxes of Sc and Al sources via measured Sc percentage in as-grown ScxAl1−xN thin films were derived as the feedback for precise determination of the ScxAl1−xN growth diagram. We identified an optimal III/N atomic flux ratio of 0.78 for smooth Sc0.18Al0.82N thin films. Further increasing the III/N ratio led to phase separation under N-rich conditions, validated by the observation of high-Sc-content hillocks with energy-dispersive X-ray spectroscopy mapping. At the fixed III/N ratio of 0.78, we found that phase separation with high-Al-content hillocks occurs for x > 0.37, which is substantially lower than the thermodynamically dictated threshold Sc content of ~0.55 in wurtzite ScxAl1−xN. We postulate that these wurtzite-phase purity degradation scenarios are correlated with adatom diffusion and the competitive incorporation process of Sc and Al. Therefore, the ScxAl1−xN growth window is severely restricted by the adatom kinetics. We obtained single crystalline Sc0.37Al0.63N thin films with X-ray diffraction (002)/(102) ω rocking curve full-width at half-maximums of 2156 arcsec and 209 arcsec and surface roughness of 1.70 nm. Piezoelectric force microscopy probing of the Sc0.37Al0.63N epilayer validates unambiguous polarization flipping by 180°.