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Abstract The objective of this study is to utilize optical coherence tomography angiography (OCTA) techniques for the purpose of identifying abnormalities in retinal and conjunctival vascular density among patients afflicted with renal hypertension. From October 2022 to October 2023, a cohort of sixteen patients diagnosed with renal hypertension (RH), comprising a total of 32 eyes, was selected from the Department of Nephrology at the First Affiliated Hospital of Nanchang University. Concurrently, a group of sixteen healthy individuals, carefully matched in characteristics, was recruited from volunteers at the Ophthalmology Research Center and designated as the healthy controls (HCs) group. Optical coherence tomography angiography was employed to assess and examine the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the macular retina in both eyes. Subsequently, a comparative analysis was conducted between the two groups, focusing on the superficial and deep retinal microvessels (MIR), macrovascular (MAR), and total microvascular (TMI). The present study employed the central annuli segmentation method (C1–C6), the hemispheric segmentation method (SL, IL, SR, IR), and the Early Treatment Diabetic Retinopathy Study (S, I, L, R) to evaluate deviations in retinal blood vessel density. The investigation aimed to examine the association between blood vessel density and TMI in conjunctival capillaries. A statistically significant difference (p

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract Background Treating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized. Results In this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p. Conclusions Our research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI.

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P

Many oil fields in the Bohai Oilfield are currently in the stage of high water cut and low recovery. Thus, it is urgent to conduct in-depth research on the potential of these oil fields to maintain stable production. After 20 years of directional well development, Bohai B Oilfield has developed a set of layers with combined production and strong injection, resulting in severe interlayer interference and difficulties in tapping the potential of the remaining oil. Owing to the limited resolution of existing seismic data, it is not possible to identify the reservoir structure inside the braided river composite sand body, including the vertical and horizontal distribution of the interlayer and thin sand body. Therefore, directional well development is currently mainly used. Here, the seismic signal harmonic frequency enhancement technology is proposed, which directly uses the fundamental component of seismic data to predict harmonic and subharmonic information, and then adds it to the original seismic data to expand the high-frequency and low-frequency seismic information, achieving the purpose of frequency enhancement. This method overcomes the limitations of traditional convolutional models, eliminating the need of well information and to estimate seismic wavelets and assume sparse stratigraphic reflection coefficients, thereby reducing the human subjective factors. The research results, verified through dynamic and static information, showed that the seismic signal harmonic frequency enhancement technology can effectively and finely identify the internal structure of braided river sand bodies, help to transform directional wells into horizontal wells for development, avoid interlayer interference, and promote efficient extraction of the remaining oil.

Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca2+, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.

AIM: To establish a meaningful standard for diagnosing ocular metastasis (OM) in menopausal breast cancer (BC) women, and explore the relationship between CA-153, CA-125, apolipoprotein A, and OM. METHODS: A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022. Women with BC who are menopausal were found to have an OM incidence of 1.6%. Furthermore, CA-153, CA-125, and apolipoprotein A (Apo A) all contributed to OM in women with BC who are postmenopausal according to binary logistic regression. Receiver operating curve (ROC) analysis was used to assess the diagnostic value of OM in patients with BC. RESULTS: Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%, whereas CA-153+Apo A illustrated the highest specificity of 99.02%. Moreover, CA-153 and CA-153+CA-125 had higher areas under the curve (AUC) of 0.973. CONCLUSION: The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC. The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.

AIM: To study functional brain abnormalities in patients with eye trauma (ET) and to discuss the pathophysiological mechanisms of ET. METHODS: Totally 31 ET patients and 31 healthy controls (HCs) were recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the functional connectivity (FC) method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Pearson's correlation analysis was used to explore the relationship between FC values in specific brain regions and clinical behaviors in patients with ET. RESULTS: Significantly increased FC between several regions was identified including the medial prefrontal cortex (MPFC) and left hippocampus formations (HF), the MPFC and left inferior parietal lobule (IPL), the left IPL and left medial temporal lobe (MTL), the left IPL and right MTL, and the right IPL and left MTL. No decreased region-to-region connectivity was detected in default mode network (DMN) sub-regions in patients with ET. Compared with HCs, ET patients exhibited significantly increased FC between several paired DMN regions, as follows: posterior cingulate cortex (PCC) and right HF (HF.R, t=2.196, P=0.032), right inferior parietal cortices (IPC.R) and left MTL (MTL.L, t=2.243, P=0.029), and right MTL (MTL.R) and HF.R (t=2.236, P=0.029). CONCLUSION: FC values in multiple brain regions of ET patients are abnormal, suggesting that these brain regions in ET patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of ET.

Abstract Background Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke. Methods We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion–reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model. Results We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1β levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1β release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy. Conclusion The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

Abstract Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1–C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

As an important component of inorganic non-metallic materials, functional glass materials mainly include electronic information glass, new energy glass, and special glass. They are the basic supporting materials for strategic emerging industries such as information display, semiconductors, new energy, deep sea, and deep space, and have become the cornerstone for the construction of an intelligent and low-carbon society in China. In recent years, China has made a series of major achievements in the field of functional glass. However, there are still problems such as prominent shortcomings of key materials, tracking research and development, decentralized innovation resources, and insufficient systematic development. In a systematic way, this study focuses on the key material technologies, industry, supports, and other systematic development elements in the field of electronic information glass, new energy glass, and special glass, and summarizes the development status of functional glass in leading countries worldwide. Considering the basic development condition of China, this study summarizes the major challenges, explores the near-, medium-, and long-term development goals, and proposes the key development directions of key functional glass materials in China. Specific suggestions include: (1) strengthening the capability to guarantee key raw materials, forming a strong support for the sustainable development of the industry; (2) accelerating the rolling planning of innovations in key functional glass materials; (3) enhancing policy support; and (4) promoting the low-carbon and digital development of key functional glass materials.

Abstract Background This study aimed to assess the impact of the pandemic of the coronavirus disease 2019 (COVID-19) on neonatology residency training in a tertiary children’s hospital in Chongqing, located in southwest China. Specifically, the study encompassed the effects on residents’ education, lived experiences, well-being, and the quality of neonatal care delivered. As higher educational institutions adapt to the post-COVID-19 era after the pandemic disruption, it is imperative that educational designers/academics learn from their experiences and challenges in curriculum design and delivery, ensuring quality and relevance in education. Methods This study employed a mixed-methods approach to investigate the influence of the COVID-19 pandemic on neonatology residency training at a tertiary children’s hospital in Chongqing. The first phase surveyed residents’ perceptions and experiences of their clinical education and well-being during the crisis. The second phase compared the quality of neonatal care between the pre-pandemic and pandemic periods. Results The survey of 123 neonatology residents examines the effects of COVID-19 on their learning, training, and mental health. The survey showed that most residents adapted well to the situation. Still, some faced challenges in their clinical education and experiences, such as reduced clinical exposure and opportunities to see rare diseases and conditions. A retrospective analysis of clinical data revealed that 7,151 neonates were admitted to the neonatology department during the study period. There was a 27.6% decrease in neonatal admissions during COVID-19, with more premature births and transfers. Residents conducted fewer clinical procedures but managed more complex cases. During COVID, hospital stays and costs were higher, but antibiotic use was lower. Although the case-mix index (CMI) score increased during the pandemic (1.25 vs. 1.18, p

Here we assess whether neuropathic pain hypersensitivity is attenuated by spinal administration of the imidazoline I1-receptor agonist LNP599 and whether the attenuation involves co-activation of α2-adrenoceptors. Spared nerve injury (SNI) model of neuropathy was used to induce mechanical hypersensitivity in male and female rats with a chronic catheter for intrathecal drug administrations. Mechanical sensitivity and heat nociception were assessed behaviorally in the injured limb. Additionally, GTPγS radioligand binding assay, β-arrestin recruitment and intracellular cAMP levels were used for receptor profiling in vitro. LNP599 (imidazoline I1 receptor agonist) and clonidine (α2-adrenoceptor agonist) produced equal dose-related mechanical antihypersensitivity effects in both sexes. LNP599 attenuated heat nociception preferentially in males, while clonidine reduced heat nociception equally in males and females. Carbophenyline (another imidazoline I1 receptor agonist) had no significant effect on mechanical hypersensitivity or heat nociception in males or females. Mechanical antihypersensitivity and heat antinociception induced by LNP599 in SNI males was prevented by pretreatments with yohimbine or atipamezole (two α2-adrenoceptor antagonists) but not by efaroxan (a mixed imidazoline I1 receptor/α2-adrenoceptor antagonist). In vitro assays indicated that LNP599 does not activate α2A- or other subtypes of α2-adrenoceptors. However, LNP599 was a weak partial agonist for 5-HT2B receptors and bound to sigma-1 and sigma-2 receptors that all are involved in modulation of spinal nociception. The results indicate that the suppression of neuropathic pain hypersensitivity by LNP599 is not due to action on spinal imidazoline I1 receptors, but rather due to indirect activation of spinal α2-adrenoceptors.

Abstract Objectives To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). Methods This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. Results Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with 5 mm tumor border ex tension and liver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor “capsule,” a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). Conclusion A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor “capsule” accurately predicted early postsurgical recurrence of a single HCC. Critical relevance statement The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor “capsule” hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. Key Points A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS. Graphical Abstract

Abstract Background Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. Methods Sprague–Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. Results Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. Conclusions Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

Abstract Background Neuroinflammation is a characteristic pathological change of Alzheimer’s Diseases (AD). Microglia have been reported to participate in inflammatory responses within the central nervous system. However, the mechanism of microglia released exosome (EXO) contribute to communication within AD microenvironment remains obscure. Methods The interaction between microglia and AD was investigated in vitro and in vivo. RNA-binding protein immunoprecipitation (RIP) was used to investigate the mechanisms of miR-223 and YB-1. The association between microglia derived exosomal YB-1/miR-223 axis and nerve cell damage were assessed using Western blot, immunofluorescence, RT-PCR, ELISA and wound healing assay. Results Here, we reported AD model was responsible for the M1-like (pro-inflammatory) polarization of microglia which in turn induced nerve cell damage. While M2-like (anti-inflammatory) microglia could release miR-223-enriched EXO which reduced neuroinflammation and ameliorated nerve damage in AD model in vivo and in vitro. Moreover, YB-1 directly interacted with miR-223 both in cell and EXO, and participated in microglia exosomal miR-223 loading. Conclusion These results indicate that anti-inflammatory microglia-mediated neuroprotection form inflammatory damage involves exporting miR-223 via EXO sorted by YB-1. Consequently, YB-1-mediated microglia exosomal sorting of miR-223 improved the nerve cell damage repair, representing a promising therapeutic target for AD.

Abstract By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

Abstract Background Influenza A virus (IAV) infection is a significant risk factor for respiratory diseases, but the host defense mechanisms against IAV remain to be defined. Immune regulators such as surfactant protein A (SP-A) and Toll-interacting protein (Tollip) have been shown to be involved in IAV infection, but whether SP-A and Tollip cooperate in more effective host defense against IAV infection has not been investigated. Methods Wild-type (WT), Tollip knockout (KO), SP-A KO, and Tollip/SP-A double KO (dKO) mice were infected with IAV for four days. Lung macrophages were isolated for bulk RNA sequencing. Precision-cut lung slices (PCLS) from WT and dKO mice were pre-treated with SP-A and then infected with IAV for 48 h. Results Viral load was significantly increased in bronchoalveolar lavage (BAL) fluid of dKO mice compared to all other strains of mice. dKO mice had significantly less recruitment of neutrophils into the lung compared to Tollip KO mice. SP-A treatment of PCLS enhanced expression of TNF and reduced viral load in dKO mouse lung tissue. Pathway analysis of bulk RNA sequencing data suggests that macrophages from IAV-infected dKO mice reduced expression of genes involved in neutrophil recruitment, IL-17 signaling, and Toll-like receptor signaling. Conclusions Our data suggests that both Tollip and SP-A are essential for the lung to exert more effective innate defense against IAV infection.

Abstract Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search method with only sequences as input. PLMSearch uses deep representations from a pre-trained protein language model and trains the similarity prediction model with a large number of real structure similarity. This enables PLMSearch to capture the remote homology information concealed behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with dissimilar sequences but similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch .

Public release of the entire Landsat data archive and cloud-based geocomputation platforms have greatly facilitated land-cover mapping worldwide. The acquisition of training samples presents a significant challenge in mapping. In this study, we have developed an approach based on transfer learning to creatively use existing global land-cover products and training samples to resolve the training sample issue. We pretrained a deep neural network (DNN) model using low-quality samples automatically generated from existing global land-cover products. The pretrained model was then fine-tuned using high-quality training samples gathered from the training samples shared by authors of existing studies. We implemented this approach to generate a land-cover map for Beijing City, China, in 2015. Using the fine-tuned DNN model, we achieved an overall accuracy (OA) of 86.4% and a kappa coefficient of 0.796, based on independent validation samples. The accuracy was the same and even surpassed that of existing land-cover maps for Beijing. The fine-tuned DNN outperformed the random forest (RF) (OA = 70.2%, kappa = 0.588) and support vector machine (SVM) models (OA = 68.7%, kappa = 0.555) using the same training samples, showing that the need for training samples in land-cover classification can be met by combining deep learning models, existing global land-cover products, and recycled training samples.

ABSTRACTMelatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.

ABSTRACT Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

Abstract Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6‐methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota‐derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota‐derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi‐omics approaches. Various antibiotics‐induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ‐free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid‐producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic‐induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

The evaluation of potato response to controlled-release fertilizers (CRFs), as a sole source of nitrogen (N) or as a blend with a soluble N source, is essential to 1) develop the best management recommendations for using CRFs in potato production and 2) provide guidelines to CRF manufacturers for developing an optimal product. This study aimed to evaluate the potato yield and quality responses to N CRFs (polymer-coated urea [PCU]) vs soluble N sources. The experiments were conducted in major potato-growing regions in the United States and China. The current industry-recommended practice of 112 kg N/ha pre-plant soil broadcast of urea plus five in-season fertigations of 224 kg N/ha as urea ammonium nitrate (UAN-32) was compared to a single pre-plant application of 224 kg N/ha as a CRF as the sole source of N or as multiple blends of CRFs and soluble N sources (i.e., urea) at various ratios. The results demonstrated that petiole nitrate_N (NO3_N) levels and tuber yield with single pre-plant broadcast applications of 224 kg N/ha as CRF/urea blends (ratio of 25/75 or 50/50) were similar to those obtained with industry-standard N management practice. N uptake and yield were significantly greater with 220 kg/ha N as the CRF than those with the same N rate as urea. Unlike the current potato industry N practice, using CRFs as either a sole source of N or blended with urea reduces the total N rate and application frequency.

PurposeThis study aimed to explore the clinical characteristics and evaluate the different types of thyroid dysfunction in babies with neonatal hyperthyroidism.MethodsThe clinical data of 19 neonates with hyperthyroidism admitted to the Children's Hospital of Chongqing Medical University between January 2012 and April 2021 were retrospectively analyzed.ResultsFifteen (78.9%) infants were born to mothers with Graves’ disease. Eleven (57.9%) infants were premature; two babies were born at small for gestational age. The age at diagnosis ranged from 3 to 34 days, with a mean of 18.53 ± 6.85 days. The majority of the babies presented with goiter (84.2%) and tachycardia (94.7%) after birth. Nine (47.4%) of them presented with abnormal weight gain, seven (36.8%) presented with stare or ocular protrusion, six (31.6%) presented with hyperexcitability, four (21.1%) presented with jaundice and liver dysfunction, two (10.5%) presented with sweating, one (5.3%) presented with fever, and one case presented without any symptoms. Transient hyperthyroidism was the main thyroid dysfunction in our study. Overt hyperthyroidism was diagnosed in 13 (68.4%) neonates. Another three babies (15.8%) presented with hyperthyroidism with slightly elevated free triiodothyronine levels, normal thyroxine (T4) levels, and low thyroid-stimulating hormone (TSH) levels. Normal thyroid hormone levels with low TSH levels were observed in three (15.8%) neonates. Ten children were treated with antithyroid drugs. Eighteen children recovered normal thyroid function at 1–3 months of age; one baby in the study group required further levothyroxine supplementation due to primary hypothyroidism (HT). One child was found to have developmental delay at 2 years of age during follow-up.ConclusionsOur study highlights the need for prolonged monitoring of thyroid function in suspected patients. A single normal screening for hyperthyroidism or the absence of a maternal history of hyperthyroidism cannot exclude this disease.

Abstract The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene‐targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug–microbiota interactions. Furthermore, we propose a new top‐down research approach to investigate the intricate nature of drug–microbiota interactions in vivo. This approach utilizes germ‐free animal models, providing foundation for the development of a new evaluation system for drug–microbiota interactions.

Abstract Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p

Lake surface water temperature (LSWT) is a crucial ecological indicator, impacting water quality, and aquatic life. Understanding its spatiotemporal trends and driving mechanisms is fundamental for lake water environment protection and management. Previous research has been limited by low-resolution satellite data and numerical simulations, hindering in-depth understanding of LSWT. This article fills the research gap by reconstructing a high-resolution LSWT dataset spanning 2000 to 2020. Employing data fusion techniques, we combined moderate resolution imaging spectroradiometer (MODIS) and Landsat observations, achieving a spatial resolution of 30 m and a revisit cycle of eight days. Seven major lakes in Yunnan Province, China, varying in urbanization intensity, were selected to investigate the impacts and mechanisms of urbanization and climate change on LSWT. The results showed that: First, the high spatiotemporal LSWT dataset reconstructed on the ubESTARFM data fusion model outperformed the existing product datasets in terms of accuracy evaluation and spatial details. Over the past 20 years, all LSWT in the study area exhibited a warming trend in both temporal and spatial dimensions; lakes in basins with higher urbanization intensity had significantly higher warming rates than the warming rates of near-surface air temperature, and the lakes showed a global warming trend. Second, the warming trend of LSWT is not only related to lake morphology and climate change, but also closely associated with urbanization; higher spatiotemporal resolution LSWT data revealed better spatiotemporal correlations between urbanization and LSWT. Third, active ecological management and enhanced watershed vegetation coverage could effectively mitigate the rate of lake warming.

Abstract Background It has been reported that Mannose-binding lectin 2 (MBL2) gene polymorphisms and expression levels are related to dilated cardiomyopathy (DCM). This study aimed to investigate the potential association between MBL2 gene polymorphisms and the pathogenesis of DCM. Methods Five single nucleotide polymorphisms (SNPs) of the MBL2 gene were genotyped in 440 DCM patients and 532 controls in Southwest China. A luciferase reporter assay was used to detect the transcriptional activity the different genotypes. MBL serum levels, left ventricle ejection fraction (LVEF) and lower left ventricular end-diastolic diameter (LVEDD) were measured. Results The rs11003125 C allele increased the transcriptional activity of the MBL2 promoter compared with the rs11003125 G allele. The rs11003125 CC carriers had higher MBL serum levels, LVEF and LVEDD than the rs11003125 CG and GG carriers. Conclusions Our study first revealed that MBL2 polymorphisms and serum MBL levels were associated with DCM. Allele C in rs11003125 of MBL2 may upregulate the expression levels of MBL. High serum MBL levels may be a protective factor in DCM pathogenesis.

AIM: To study retinal microvascular and microstructural alterations in meibomian gland dysfunction (MGD) in severely obese population using optical coherence tomography angiography (OCTA). METHODS: Twelve MGD patients with severely obese population (PAT group; 24 eyes) and 12 healthy controls (HC group; 24 eyes) were recruited. OCTA images were segmented into five [superior (S), nasal (N), inferior (I), temporal (T), and central foveal (C)] or nine [inner superior (IS), outer superior (OS), inner nasal (IN), outer nasal (ON), inner inferior (II), outer inferior (OI), inner temporal (IT), outer temporal (OT), and C] subregions. The superficial vessel density (SVD), retinal thickness (RT), foveal avascular zone (FAZ) parameters, and retinal volume were measured. RESULTS: Visual acuity was significantly different between two groups (0.8±0.17 in PAT group vs 0.2±0.06 in HC group). SVD was significantly lower in PATs in N, T, OS, IN, OT, and ON. The area under the receiver operating characteristic curve (AUC) for T was 0.961 [95% confidence interval (CI): 0.908 to 1.000], for OS was 0.962 (95%CI: 0.915 to 1.000). RT was significantly lower in PATs in IS, OS, OI, OT, ON, IT, IN, and II. AUC for OT was 0.935 (95%CI: 0.870 to 0.999), for IS was 0.915 (95% CI: 0.838 to 0.992). Angiography results showed significantly lower area and perimeter of FAZ, SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group. CONCLUSION: Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures. These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

ABSTRACTPoint clouds are widely used in Earth surface research but usually exhibit gaps of missing data. Previous point cloud restoration methods used in terrain modelling have not fully considered complex terrain characteristics, which can be summarised as the controlling role of topographic features in shaping terrain surfaces and the inherent similarities observed among these surfaces. This work introduces a novel method that integrates Topographic Features and Patch Matching (TFPM) into point cloud restoration processes for terrain modelling. The method mainly contains three steps. First, identifying gap boundary points. Second, topographic feature points are extracted and subsequently interpolated into the identified gaps. Third, searching other parts of the raw point cloud for patches resembling the gaps, and the identified patches are used as templates to restore the point cloud. The proposed method is benchmarked against three state-of-the-art point cloud restoration methods. The experimental results demonstrate that the TFPM method consistently exhibits superior accuracy in terrain modelling and analysis, as evidenced by low values of the root mean square error, average elevation difference, and average slope difference. This work endeavours to incorporate topographic features into point cloud restoration processes and can benefit future research related to terrain modelling and analysis.

The semantic segmentation of informal urban settlements represents an essential contribution towards renovation strategies and reconstruction plans. In this context, however, a big challenge remains unsolved when dealing with incomplete data acquisitions from multiple sensing devices, especially when study areas are depicted by images of different resolutions. In practice, traditional methodologies are directed to downgrade the higher-resolution data to the lowest-resolution measure, to define an overall homogeneous dataset, which is however ineffective in downstream segmentation activities of such crowded unplanned urban environments. To this purpose, we hereby tackle the problem in the opposite direction, namely upscaling the lower-resolution data to the highest-resolution measure, contributing to assess the use of cutting-edge super-resolution generative adversarial network (SR-GAN) architectures. The experimental novelty targets the particular case involving the automatic detection of ‘urban villages’, sign of the quick transformation of Chinese urban environments. By aligning image resolutions from two different data sources (Gaofen-2 and Sentinel-2 data), we evaluated the degree of improvement with regard to pixel-based landcover segmentation, achieving, on a 1 m resolution target, classification accuracies up to 83%, 67% and 56% for 4x, 8x, and 10x resolution upgrades respectively, disclosing the advantages of artificially-upscaled images for segmenting detailed characteristics of informal settlements.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

The ceRNA network, consisting of both noncoding RNA and protein-coding RNA, governs the occurrence, progression, metastasis, and infiltration of lung adenocarcinoma. Signatures comprising multiple genes can effectively determine survival stratification and prognosis of patients with lung adenocarcinoma. To explore the mechanisms of lung adenocarcinoma progression and identify potential biological targets, we carried out systematic bioinformatics analyses of the genetic profiles of lung adenocarcinoma, such as weighted gene co-expression network analysis (WGCNA), differential expression (DE) assessment, univariate and multivariate Cox proportional hazard regression models, ceRNA modulatory networks generated using the ENCORI and miRcode databases, nomogram models, ROC curve assessment, and Kaplan-Meier survival curve analysis. The ceRNA network encompassed 37 nodes, comprising 12 mRNAs, 22 lncRNAs, and three miRNAs. Simultaneously, we performed integration analysis using the 12 genes from the ceRNA network. Our findings revealed that the signature established by these 12 genes serves as an adverse element in lung adenocarcinoma, contributing to unfavorable patient prognosis. To ensure the credibility of our results, we used in vitro experiments for further verification. In conclusion, our study delved into the potential mechanisms underlying lung adenocarcinoma via the ceRNA regulatory network, specifically focusing on the PIF1 and has-miR-125a-5p axis. Additionally, a signature comprising 12 genes was identified as a biomarker related to the prognosis of lung adenocarcinoma.

Abstract Bacterial meningitis (BM) is potentially life threatening in neonates, but the duration of antibiotic therapy is not well established. We aimed to compare the efficacy and safety among neonates suffering from BM of a relatively shortened duration of antibiotic treatment to the currently recommended course. We did a retrospective cohort study in neonates (gestational age [GA] or corrected GA ≥35 weeks) diagnosed with BM. Neonates in the study group were assigned to withdraw the antibiotics on condition that they were clinically stable after taking sufficient antibiotics with normal serological inflammatory biomarkers, whereas the cerebrospinal fluid (CSF) indicators remain abnormal. Neonates in the control group were treated until both serological and CSF indicators returned to normal as recommended. The incidence of recurrent infection after the discontinuation of antibiotics and adverse drug reactions (ADRs) during hospitalization was measured. A total of 233 neonates were enrolled, of whom 160 were assigned to a shortened antibiotic duration and 73 were treated according to the current guidelines. Twelve patients (7.5%) relapsed in the study group, whereas 4 (5.5%) relapsed in the control group (χ2 = 0.320, p = 0.572). The incidences of ADRs were similar in both groups (p > 0.05). The study indicates that antibiotics might be safely discontinued in neonates (GA ≥35 weeks) diagnosed with BM who are clinically stable or improving after antibiotic treatment and feature normal serological inflammatory markers, no severe complications, and no evidence of systemic infection, even if CSF parameters are not completely normal.

Rationale and objectivesTo construct a predictive model for benign and malignant peripheral pulmonary lesions (PPLs) using a random forest algorithm based on grayscale ultrasound and ultrasound contrast, and to evaluate its diagnostic value.Materials and methodsWe selected 254 patients with PPLs detected using chest lung computed tomography between October 2021 and July 2023, including 161 malignant and 93 benign lesions. Relevant variables for judging benign and malignant PPLs were screened using logistic regression analysis. A model was constructed using the random forest algorithm, and the test set was verified. Correlations between these relevant variables and the diagnosis of benign and malignant PPLs were evaluated.ResultsAge, lesion shape, size, angle between the lesion border and chest wall, boundary clarity, edge regularity, air bronchogram, vascular signs, enhancement patterns, enhancement intensity, homogeneity of enhancement, number of non-enhancing regions, non-enhancing region type, arrival time (AT) of the lesion, lesion-lung AT difference, AT difference ratio, and time to peak were the relevant variables for judging benign and malignant PPLs. Consequently, a model and receiver operating characteristic curve were constructed with an AUC of 0.92 and an accuracy of 88.2%. The test set results showed that the model had good predictive ability. The index with the highest correlation for judging benign and malignant PPLs was the AT difference ratio. Other important factors were lesion size, patient age, and lesion morphology.ConclusionThe random forest algorithm model constructed based on clinical data and ultrasound imaging features has clinical application value for predicting benign and malignant PPLs.

Abstract RNA 3D structure prediction is a long-standing challenge. Inspired by the recent breakthrough in protein structure prediction, we developed trRosettaRNA, an automated deep learning-based approach to RNA 3D structure prediction. The trRosettaRNA pipeline comprises two major steps: 1D and 2D geometries prediction by a transformer network; and 3D structure folding by energy minimization. Benchmark tests suggest that trRosettaRNA outperforms traditional automated methods. In the blind tests of the 15th Critical Assessment of Structure Prediction (CASP15) and the RNA-Puzzles experiments, the automated trRosettaRNA predictions for the natural RNAs are competitive with the top human predictions. trRosettaRNA also outperforms other deep learning-based methods in CASP15 when measured by the Z-score of the Root-Mean-Square Deviation. Nevertheless, it remains challenging to predict accurate structures for synthetic RNAs with an automated approach. We hope this work could be a good start toward solving the hard problem of RNA structure prediction with deep learning.

Abstract Objective To evaluate the association between traditional laboratory findings and death, and to find risk factors for death in infants with early onset sepsis (EOS). Study design This was a single-center, case–control, retrospective trial conducted between January 2020 and August 2021. Infants with EOS were enrolled and divided into two groups based on outcome before hospital discharge: non-survivors (Mortality group) and survivors (Survival group). Results Out of 556 eligible neonates, there were 38 (6.8%) deaths. After univariate analysis and ROC curve analysis, there were a total of 12 values with significant differences (p 0.001), septic shock (OR = 6.15, 95% CI [2.52, 15.00], p 0.001), serum lactic acid (OR = 0.82, 95%CI[0.75, 0.90], p 0.001) could be regarded as risk factors for death with 94.0% correct predictions. Conclusions The factors affecting the prognosis of EOS in neonates were BW, PPHN, septic shock, heart failure, serum lactic acid, and AST. Timely correction of these modifiable risk factors for death may decrease the mortality of EOS in neonates.

Abstract In the context of the digital economy, understanding the impact of digital participation on farmers’ environmental behavior is crucial for promoting environmental literacy and improving quality of life. This study focuses on the influence of internet use on domestic waste sorting among farm households in rural areas of eastern, central, and western China, based on data from a micro survey conducted in 2126 households. The study utilizes an ordered probability model to examine the impact of internet use on waste sorting behavior and explores any heterogeneity in this relationship. The results reveal that internet use significantly increases the likelihood of farmers participating in domestic waste sorting. This finding remains consistent even after conducting robustness tests. Furthermore, the study demonstrates that internet use reduces the probability of non-participation in waste separation by 14.9%, while increasing the proportion of waste sorting into two, three, and four categories by 3.86, 5.99, and 5.04%, respectively. In other words, farmers who use the internet are more likely to engage in proper waste separation practices. Heterogeneity analysis indicates that the promotion of internet use facilitates information access for traditionally marginalized groups, such as women, older individuals, those with low income, and those with low education levels. Consequently, these groups are more likely to participate in household waste sorting. This study serves as an important reference for developing countries and regions that aim to enhance residential waste participation through internet use.

Abstract Background Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. Methods Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan–Meier and log-rank methods were used to evaluate survival outcomes. Results In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including “rim arterial phase hyperenhancement” (OR = 5.9, 95% confidence interval [CI]: 2.9–12.0, 10 points), “nodule in nodule architecture” (OR = 3.5, 95% CI: 2.1–5.9, 7 points), “non-smooth tumor margin” (OR = 1.6, 95% CI: 0.8–2.9, 3 points), and “non-peripheral washout” (OR = 0.6, 95% CI: 0.3–1.0, − 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p

Abstract Background Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). Methods We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non‐ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p

Abstract To study the damage mechanism of multi‐anchor piles in tunnel crossing landslide area under earthquake, the damping performance of multi‐anchor piles was discussed. The energy dissipation springs were used as the optimization device of the anchor head to carry out the shaking table comparison test on the reinforced slope. The Hilbert spectrum and Hilbert marginal spectrum were proposed to analyze the seismic damage mechanism of the multi‐anchor piles, and the peak Fourier spectrum amplitude (PFSA) was used to verify the effectiveness of the method. The results show that the seismic energy is concentrated in the high‐frequency component (30–40 Hz) of the Hilbert spectrum and the low‐frequency component (12–30 Hz) of the marginal spectrum. This indicates that they can be combined with the distribution law of the PFSA to identify the overall and local dynamic responses of the multi‐anchored piles, respectively. The stretchable deformation of the energy‐dissipation springs improves the coordination of the multi‐anchor piles, resulting in better pile integrity. The damage mechanism of the multi‐anchor piles is elucidated based on the energy method: local damage at the top and middle areas of the multi‐anchor piles is mainly caused by the low‐frequency component (12–30 Hz) of the marginal spectrum under the action of 0.15g and 0.20g seismic intensities. As the seismic intensity increases to 0.30g, the dynamic response of the slope is further amplified by the high‐frequency component (30–40 Hz) of the Hilbert energy spectrum, which leads to the overall damage of the multi‐anchor piles.

Abstract Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8+, CD4+, and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8+ T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.