Tumor necrosis serves as an important pathological characteristic of stage I-II colon cancer.

BACKGROUND: The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. MATERIALS AND METHODS: In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). CONCLUSIONS: The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Salivary metabolites are promising noninvasive biomarkers of drug-induced liver injury.

BACKGROUND: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests. AIM: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools. METHODS: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves. RESULTS: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1). CONCLUSION: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed.

Detunable wireless resonator arrays for TMJ MRI: A comparative study.

Temporomandibular Joint Magnetic Resonance Imaging (TMJ MRI) is crucial for diagnosing temporomandibular disorders (TMDs). This study advances the use of inductively coupled wireless coils to enhance imaging quality in TMJ MRI. After investigating multiple wireless resonator configurations, including a 1-loop design with a loop diameter of 9 cm, a 2-loop design with each loop having a diameter of 7 cm, and a 3-loop design with each loop having a diameter of 5 cm, our findings indicate that the 3-loop configuration achieves the optimal signal-to-noise ratio (SNR), surpassing other wireless arrays. Bilateral deployment of wireless coils further amplifies SNR, enabling superior visualization of TMJ structures, particularly with the 3-loop design. This cost-effective and comfortable solution, featuring a detunable design, eliminates the need for system parameter adjustments. The study indicates broad adaptability across MRI platforms, enhancing TMJ imaging for routine clinical diagnostics of TMDs.

The secondary prevention of coronary heart disease in US adults 75 Years and older in daily practice: Results from the National Health and Nutrition Examination Survey 1999-2018 survey.

Background: Pharmacologic therapies, risk factor control, and lifestyle alterations were independently proven to reduce long-term cardiovascular events. However, comprehensive research examining the extent to which individuals aged 75 and above in the United States adhere to national guidelines for the secondary prevention of coronary heart disease is limited. Therefore, the primary objective of this study was to examine the current state of secondary prevention of coronary heart disease in persons 75 years of age and older in the United States and to examine the factors that contribute to inadequate drug utilization and poor control of numerous risk factors. Methods: We identified patients over 75 years of age with coronary heart disease based on the National Health and Nutrition Examination Survey from 1999 to 2018 and analyzed the adequacy of risk factor control and adherence to lifestyle and medication recommendations to assess the effectiveness of coronary heart disease management. Logistic regression analysis was used to identify factors associated with uncontrolled risk factors or noncompliance with recommended medications. Results: We collected information from 1566 known coronary heart disease patients aged ≥75 years of age. The majority were at target goals for blood pressure (58.88%), low-density lipoprotein cholesterol (66.85%), and glycated hemoglobin (76.12%). Only 27.8% and 36.06% were at targets for body mass index and waist circumference, respectively. 91.95% reported smoking cessation, 85.98% followed recommended alcohol consumption, whereas only 10.34% reported sufficient physical activity. For ß blockers, angiotensin -converting enzyme inhibitors/angiotensin receptor blockers, statins, and antiplatelet drugs, the utilization of indicated therapy was 54.41%, 49.36%, 54.79%, and 19.03%, respectively (6.26% for all 4 medications). The results of the logistic regression analysis demonstrated that diabetes mellitus and metabolic syndrome were critical markers of numerous uncontrolled risk variables as well as noncompliance with medication regimens. Conclusions: A vast majority of coronary heart disease patients ≥75 years in the USA exhibited suboptimal overall control of critical coronary heart disease risk factors. For this patient population, more knowledge is necessary to enable patients to receive continuous support, guidance, and counseling.

The contribution of small heterodimer partner to the occurrence and progression of cholestatic liver injury.

BACKGROUND AND AIM: Small heterodimer partner (SHP, encoded by NR0B2) plays an important role in maintaining bile acid homeostasis. The loss of the hepatic farnesoid X receptor (FXR)/SHP signal can cause severe cholestatic liver injury (CLI). FXR and SHP have overlapping and nonoverlapping functions in bile acid homeostasis. However, the key role played by SHP in CLI is unclear. METHODS: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model was established. The effect of SHP knockout (SHP-KO) on liver and ileal pathology was evaluated. 16S rRNA gene sequencing analysis combined with untargeted metabolomics was applied to reveal the involvement of SHP in the pathogenesis of CLI. RESULTS: The results showed that ANIT (75 mg/kg) induced cholestasis in WT mice. No significant morphological changes were found in the liver and ileal tissue of SHP-KO mice. However, the serum metabolism and intestinal flora characteristics were significantly changed. Moreover, compared with the WT + ANIT group, the serum levels of ALT and AST in the SHP-KO + ANIT group were significantly increased, and punctate necrosis in the liver tissue was more obvious. The ileum villi showed obvious shedding, thinning, and shortening. In addition, SHP-KO-associated differential intestinal flora and differential biomarkers were significantly associated. CONCLUSION: In this study, we elucidated the serum metabolic characteristics and intestinal flora changes related to the aggravation of CLI in SHP-KO mice induced by ANIT.

Engineering pineapple peel cellulose nanofibrils with oxidase-mimic functionalities for antibacterial and fruit preservation.

In this study, an antibacterial material (CNF@CoMn-NS) with oxidase-like activity was created using ultrathin cobalt­manganese nanosheets (CoMn-NS) with a larger specific surface area grown onto pineapple peel cellulose nanofibrils (CNF). The results showed that the CoMn-NS grew well on the CNF, and the obtained CNF@CoMn-NS exhibited good oxidase-like activity. The imidazole salt framework of the CNF@CoMn-NS contained cobalt and manganese in multiple oxidation states, enabling an active redox cycle and generating active oxygen species (ROS) such as singlet molecular oxygen atoms (1O2) and superoxide radical (·O2-), resulting in the significant inactivation of Staphylococcus aureus (74.14%) and Escherichia coli (54.87%). Importantly, the CNF@CoMn-NS did not exhibit cytotoxicity. The CNF@CoMn-NS further self-assembled into a CNF@CoMn-NS paper with flexibility, stability, and antibacterial properties, which can effectively protect the wound of two varieties of pears from decay caused by microorganisms. This study demonstrated the potential of using renewable and degradable CNF as substrate combined with artificial enzymes as a promising approach to creating antibacterial materials for food preservation and even extending to textiles and biomedical applications.

A Multistate Thermoresponsive Smart Window Based on a Multifunctional Luminescent Solar Concentrator.

Conventional luminescent solar concentrators (LSCs) usually only have the ability to absorb solar energy and convert it to electricity but are not able to regulate the transmitted light. Herein, a multistate thermoresponsive smart window (SW) based on LSC has been fabricated, in which the stimuli-responsive host layer consists of polydimethylsiloxane (PDMS) and ethylene glycol solution (EGS) microdroplets stacking with LSC layer-based on near-infrared (NIR) CuInSe2-xSx/ZnS core/shell quantum dots (QDs) and PDMS matrix. As-synthesized CISSe/ZnS QDs with broad NIR absorption in LSC exhibit controllable emission spectra over 833-1088 nm and high photoluminescence (PL) quantum yield from 45 to 83%. Coupling with Si solar cells as a reference, optimized LSC-SW devices with dimensions of 5 × 5 × 0.9 cm3 exhibit higher power conversion efficiency (PCE) of 1.19-1.36% with increased temperature from 0 to 50 °C than those of sole LSC and SW devices. The corresponding visible light transmissions are regulated from 75.1 to 48.1% accordingly. The improvement of PCEs in an opaque state is mainly due to enhanced absorption of QDs originating from rescattered photons from the EGS/PDMS layer, leading to more emitted photons reaching photovoltaics. This work is expected to bring up new opportunities for applications in greenhouses, building facades, and energy-efficient smart windows.

A detunable wireless resonator insert for high-resolution TMJ MRI at 1.5 T.

MRI is essential for evaluating and diagnosing various conditions affecting the temporomandibular joint (TMJ) and surrounding structures, as it provides highly detailed images that enable healthcare professionals to assess the joints and surroundings in great detail. While commercial MRI scanners typically come equipped with basic receive coils, such as the head receive array, RF coils tailored for specialized applications like TMJ MRI must be obtained separately. Consequently, TMJ MRI scans are often conducted using the head receive array, yet this configuration proves suboptimal due to the lack of specialized coils. In this study, we introduce a simple, low-cost, and easy-to-reproduce wireless resonator insert to enhance the quality of TMJ MRI at 1.5 T. The wireless resonator shows a significant improvement in signal-to-noise ratio (SNR) and noticeably better imaging quality than the head array alone configuration in both phantom and in vivo images.

Oral and maxillofacial surgeons' views on the adoption of additive manufacturing: findings from a nationwide survey.

OBJECTIVES: Hospitals in many European countries have implemented Additive Manufacturing (AM) technology for multiple Oral and Maxillofacial Surgery (OMFS) applications. Although the technology is widely implemented, surgeons also play a crucial role in whether a hospital will adopt the technology for surgical procedures. The study has two objectives: (1) to investigate how hospital type (university or non-university hospital) influences surgeons' views on AM, and (2) to explore how previous experience with AM (AM experience or not) influences surgeons' views on AM. MATERIALS AND METHODS: An online questionnaire to capture surgeons' views was designed, consisting of 11 Likert scale questions formulated according to the Consolidated Framework for Implementation Research (CFIR). The questionnaire was sent to OMF surgeons through the channel provided by the Association of Oral and Maxillofacial Surgery in Sweden. Data were analyzed using the Mann-Whitney U test to identify significant differences among OMF surgeons in terms of organizational form (i.e., university hospital or non-university hospital) and experience of AM (i.e., AM experience or no-experience). RESULTS: In total, 31 OMF surgeons responded to the survey. Views of surgeons from universities and non-universities, as well as between surgeons with experience and no-experience, did not show significant differences in the 11 questions captured across five CFIR domains. However, the "individual characteristics" domain in CFIR, consisting of three questions, did show significant differences between surgeons' experience with AM and no-experience (P-values: P = 0.01, P = 0.01, and P = 0.04). CONCLUSIONS: Surgeons, whether affiliated with university hospitals or non-university hospitals and regardless of their prior experience with AM, generally exhibit a favorable attitude towards AM. However, there were significant differences in terms of individual characteristics between those who had prior experience with AM and those who did not. CLINICAL RELEVANCE: This investigation facilitates the implementation of AM in OMFS by reporting on the views of OMF surgeons on AM.

Correlation between serum biomarkers, brain volume, and retinal neuronal loss in early-onset Alzheimer's disease.

PURPOSE: To compare the peripapillary retinal nerve fiber layer (pRNFL), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) thickness measurement in early-onset Alzheimer's disease (EOAD) and controls using spectral domain optical coherence tomography (SD-OCT). We also assessed the relationship between SD-OCT measurements and cognitive measures, serum biomarkers for Alzheimer's disease (AD), and cerebral microstructural volume. METHODS: pRNFL, RNFL, and GCC thicknesses were measured in 43 EOAD and 42 controls using SD-OCT. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status, magnetic resonance imaging (MRI) tool was used to quantify cerebral microstructural volume, and serum biomarkers were quantified from peripheral blood. RESULTS: EOAD patients had thinner pRNFL (P < 0.001), RNFL (P = 0.008), and GCC (P = 0.018) thicknesses compared to controls after adjusting for multiple factors. pRNFL thickness correlated (P = 0.016) with serum t-tau level. Serum Aß42 (P < 0.05) concentration correlated with RNFL thickness. Importantly, occipital lobe volume (P = 0.010) correlated with GCC thicknesses in EOAD patients. CONCLUSION: Our findings suggest that retinal thickness may be useful markers for assessing neurodegenerative process in EOAD.

Contextualizing the revised Patient Perception of Patient-Centeredness (PPPC-R) scale in primary healthcare settings: a validity and reliability evaluation study.

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P < 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach's α also indicated good internal consistency reliability: The overall Cronbach's α was 0.922, and the Cronbach's α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality.

Accurate Robot Arm Attitude Estimation Based on Multi-View Images and Super-Resolution Keypoint Detection Networks.

Robot arm monitoring is often required in intelligent industrial scenarios. A two-stage method for robot arm attitude estimation based on multi-view images is proposed. In the first stage, a super-resolution keypoint detection network (SRKDNet) is proposed. The SRKDNet incorporates a subpixel convolution module in the backbone neural network, which can output high-resolution heatmaps for keypoint detection without significantly increasing the computational resource consumption. Efficient virtual and real sampling and SRKDNet training methods are put forward. The SRKDNet is trained with generated virtual data and fine-tuned with real sample data. This method decreases the time and manpower consumed in collecting data in real scenarios and achieves a better generalization effect on real data. A coarse-to-fine dual-SRKDNet detection mechanism is proposed and verified. Full-view and close-up dual SRKDNets are executed to first detect the keypoints and then refine the results. The keypoint detection accuracy, PCK@0.15, for the real robot arm reaches up to 96.07%. In the second stage, an equation system, involving the camera imaging model, the robot arm kinematic model and keypoints with different confidence values, is established to solve the unknown rotation angles of the joints. The proposed confidence-based keypoint screening scheme makes full use of the information redundancy of multi-view images to ensure attitude estimation accuracy. Experiments on a real UR10 robot arm under three views demonstrate that the average estimation error of the joint angles is 0.53 degrees, which is superior to that achieved with the comparison methods.

Calcineurin B-like protein ZmCBL8-1 promotes salt stress resistance in Arabidopsis.

MAIN CONCLUSION: ZmCBL8-1 enhances salt stress tolerance in maize by improving the antioxidant system to neutralize ROS homeostasis and inducing Na+/H+ antiporter gene expressions of leaves. Calcineurin B-like proteins (CBLs) as plant-specific calcium sensors have been explored for their roles in the regulation of abiotic stress tolerance. Further, the functional variations in ZmCBL8, encoding a component of the salt overly sensitive pathway, conferred the salt stress tolerance in maize. ZmCBL8-1 is a transcript of ZmCBL8 found in maize, but its function in the salt stress response is still unclear. The present study aimed to characterize the protein ZmCBL8-1 that was determined to be composed of 194 amino acids (aa) with three conserved EF hands responsible for binding Ca2+. However, a 20-aa fragment was found to be missing from its C-terminus relative to another transcript of ZmCBL8. Results indicated that it harbored a dual-lipid modification motif MGCXXS at its N-terminus and was located on the cell membrane. The accumulation of ZmCBL8-1 transcripts was high in the roots but relatively lower in the leaves of maize under normal condition. In contrast, its expression was significantly decreased in the roots, while increased in the leaves under NaCl treatment. The overexpression of ZmCBL8-1 resulted in higher salt stress resistance of transgenic Arabidopsis in a Ca2+-dependent manner relative to that of the wild type (WT). In ZmCBL8-1-overexpressing plants exposed to NaCl, the contents of malondialdehyde and hydrogen peroxide were decreased in comparison with those in the WT, and the expression of key genes involved in the antioxidant defense system and Na+/H+ antiporter were upregulated. These results suggested that ZmCBL8-1 played a positive role in the response of leaves to salt stress by inducing the expression of Na+/H+ antiporter genes and enhancing the antioxidant system to neutralize the accumulation of reactive oxygen species. These observations further indicate that ZmCBL8-1 confers salt stress tolerance, suggesting that transcriptional regulation of the ZmCBL8 gene is important for salt tolerance.

Adoption of additive manufacturing in oral and maxillofacial surgery among university and non-university hospitals in Sweden: findings from a nationwide survey.

PURPOSE: Additive manufacturing (AM) is an innovative printing technology that can manufacture 3-dimensional solid objects by adding layers of material from model data. AM in oral and maxillofacial surgery (OMFS) provides several clinical applications such as surgical guides and implants. However, the adoption of AM in OMFS is not well covered. The purpose was to study the adoption of AM in OMFS in university and non-university hospitals in Sweden. Three research questions were addressed: What is the degree of using AM solutions in university and non-university hospitals?; What are AM solutions used?; How are the AM solutions accessed (production mode) in university hospitals and non-university hospitals? METHODS: A survey was distributed to OMF surgeons in Sweden. The questionnaire consisted of 16 questions. Data were analyzed through descriptive and content analysis. RESULTS: A total of 14 university and non-university hospitals were captured. All 14 hospitals have adopted AM technology and 11 of the hospitals adopted AM in OMFS. Orthognathic and trauma surgery are two major types of surgery that involve AM technology where material extrusion and vat polymerization are the two most used AM technologies in OMFS. The primary application of AM was in medical models and guides. CONCLUSION: Majority of Swedish university hospitals and non-university hospitals have adopted AM in OMFS. The type of hospital (university or non-university hospital) has no impact on AM adoption. AM in OMFS in Sweden can be perceived to be a mature clinical application.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Dual-Ligand Strategy to Construct Metal Organic Gel Catalyst with the Optimized Electronic Structure for High-Efficiency Overall Water Splitting and Flexible Metal-Air Battery.

Non-noble metal catalysts are known for their efficient catalytic performance for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). Metal organic gels (MOGs) can be considered as a promising electrocatalyst owing to the diverse physicochemical properties but usually suffer from its poor electrical conductivity and catalytic stability. Here, a FeCo-MOG is constructed with considerable trifunctional activity. The optimal P-CoFe-H3 prepared by using phytic acid (PA) and 2,4,6-Tris[(p-carboxyphenyl)amino]-1,3,5-triazine benzoic acid (H3TATAB) as dual ligands), exhibits outstanding ORR, OER, and HER activities as well as stability, exceeding most of state-of-the-art catalysts. As expected, the flexible Zn-air battery applied with P-CoFe-H3 as air cathode displays considerable power density, discharge voltage plateau, and cycling stability. Impressively, it is also capable of driving the overall water-splitting device by applying the P-CoFe-H3 as anode and cathode. Furthermore, theoretical calculations reveal that dual ligands can optimize the coordination environment and charge density of active sites, thereby reducing the absorption energy of intermediate species and boosting the catalytic performance. This work endows the dual-ligands coordination strategy with great potentiality for MOGs-based electrocatalysts in energy conversion devices.

Integrated network pharmacology and metabolomics to investigate the effects and possible mechanisms of Dehydroevodiamine against ethanol-induced gastric ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetradium ruticarpum (A.Juss.) T.G.Hartley, a traditional Chinese medicine with thousands of years of medicinal history, has been employed to address issues such as indigestion, abdominal pain, and vomiting. Dehydroevodiamine (DHE) is a quinazoline alkaloid extracted from traditional Chinese medicine Tetradium ruticarpum (A.Juss.) T.G.Hartley. Previous studies have shown that DHE has anti-inflammatory, analgesic, and antioxidant activities. However, it is still unclear whether DHE has an effect on ethanol-induced gastric ulcers. AIM OF THE STUDY: The objective of this study is to investigate the therapeutic efficacy and underlying mechanisms of action of DHE on ethanol-induced gastric ulcers using network pharmacology and metabolomics strategies. METHODS: In this study, we used ethanol-induced rats as a model to assess the efficacy of DHE by biochemical indicator assays and pathological tissue detection. The integration of network pharmacology and metabolomics was used to explore possible mechanisms and was validated by western blot experiments. Finally, molecular docking was used to analyze the binding energy between DHE and the targets of PIK3CG and PLA2G2A. RESULTS: DHE was able to reverse ethanol-induced abnormalities in biochemical indicators and improve pathological tissue. Network pharmacology results indicated that DHE may be involved in the regulation of gastric ulcers by modulating 79 targets, and metabolomics results showed that a total of 13 metabolites were changed before and after DHE administration. Integrating network pharmacology and metabolomics, PIK3CG and PLA2G2A were identified as possible targets to exert therapeutic effects. In addition, the MAPKs pathway may also be involved in the regulation of ethanol-induced gastric ulcers. Finally, molecular docking results showed that DHE had low binding energies with both PIK3CG and PLA2G2A. CONCLUSIONS: These findings suggest that DHE was able to exert a protective effect against ethanol-induced gastric ulcers by modulating multiple metabolites with multiple targets. This study provides a valuable reference for the development of antiulcer drugs.

Unveiling the power of microenvironment in liver regeneration: an in-depth overview.

The liver serves as a vital regulatory hub for various physiological processes, including sugar, protein, and fat metabolism, coagulation regulation, immune system maintenance, hormone inactivation, urea metabolism, and water-electrolyte acid-base balance control. These functions rely on coordinated communication among different liver cell types, particularly within the liver's fundamental hepatic lobular structure. In the early stages of liver development, diverse liver cells differentiate from stem cells in a carefully orchestrated manner. Despite its susceptibility to damage, the liver possesses a remarkable regenerative capacity, with the hepatic lobule serving as a secure environment for cell division and proliferation during liver regeneration. This regenerative process depends on a complex microenvironment, involving liver resident cells, circulating cells, secreted cytokines, extracellular matrix, and biological forces. While hepatocytes proliferate under varying injury conditions, their sources may vary. It is well-established that hepatocytes with regenerative potential are distributed throughout the hepatic lobules. However, a comprehensive spatiotemporal model of liver regeneration remains elusive, despite recent advancements in genomics, lineage tracing, and microscopic imaging. This review summarizes the spatial distribution of cell gene expression within the regenerative microenvironment and its impact on liver regeneration patterns. It offers valuable insights into understanding the complex process of liver regeneration.

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults.

Purpose: We explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort. Methods: This observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (µm) were measured on the OCT tool. Results: Older adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p < 0.05) between GCIPL and PWMH and total WMH was observed in our older adults. Conclusion: Both GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline.