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Yan Pan, Wei Dong Chen, Lei Liu, Huijuan Yang, Baochao Chang, Caixia Cui Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, People’s Republic of ChinaCorrespondence: Wei Dong Chen, Email cwd2012@163.comObjective: Serum-specific antibodies as a non-invasive means to effectively diagnose idiopathic membranous nephropathy and assess clinicopathology.Methods: Immunofluorescence of anti-PLA2R and THSD7A antibodies and kidney tissue PLA2R, THSD7A and IgG4 expression in IMN and non-IMN (2020– 2021) was detected to assess the efficacy of diagnosing IMN. IMN patients were divided into two groups, anti-PLA2R antibody positive (161 cases) and negative (26 cases), and two groups, kidney tissue PLA2R (40 cases) and PLA2R+THSD7A (6 cases), to compare the clinical and pathological features, and to carry out a prognostic analysis of THSD7A-positive patients, with a focus on correlation with malignancy.Results: The positive rate of anti-PLA2R antibodies was significantly higher in IMN (P< 0.05); anti-PLA2R antibodies, kidney tissue PLA2R and IgG4 and THSD7A had some diagnostic value. Anti-PLA2R antibodies correlated with proteinuria levels in IMN patients, and their levels were negatively correlated with blood albumin (r=− 0.146, P=0.042); correlated with pathological stage and C3 and IgG4 immunodeposition; there was no significant difference in clinical pathology between kidney tissue THSD7A+PLA2R positive compared to kidney tissue PLA2R positive patients, but the probability of achieving complete remission was low and time longer, and no malignancy events were detected during follow-up.Conclusion: Anti-PLA2R antibodies, kidney tissue PLA2R, THSD7A and IgG4 have high diagnostic efficacy for IMN; anti-PLA2R antibodies can be used as diagnostic markers to assist in the assessment of clinical and pathological features; co-expression of kidney tissue PLA2R and THSD7A is not significantly different from kidney tissue PLA2R in assessing the clinical features, pathological manifestations and prognosis, but requires long-term. However, long-term follow-up is needed to monitor the potential risk, and a larger multicentre study with long-term follow-up is expected to be conducted to comprehensively assess IMN characteristics.Keywords: Idiopathic membranous nephropathy, PLA2R, THSD7A, clinical features and pathology

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

Shan Qiao,1,2,&ast; Haiyun Li,3,&ast; Caisan Cui,4 Chong Zhang,1 Aihua Wang,1 Wenjing Jiang,3 Shanchao Zhang1,5 1Department of Neurology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanchao Zhang, Email zhangshanchao2012@163.com; Wenjing Jiang, Email jiangwenjing@qiluhospital.comPurpose: CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E).Patients and Methods: The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes.Results: 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with > 40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age < 60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1β, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb.Conclusion: Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1β, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.Keywords: autoimmune encephalitis, cytokines, neuroinflammation, cerebrospinal fluid

We propose a new classification model—a new classification model for clustering overlapping problems based on K-Means and neural networks. K-means clustering algorithm belongs to unsupervised learning. It is a classic algorithm for solving clustering problems. Since this algorithm calculates its categories based on distance, the results tend to converge to the local optimal solution and have poor boundary clustering properties. The K-Means classification algorithm defines clusters by the distance between the cluster center value and the target object, and the optimal result is obtained through continuous iteration. Therefore, clustering results are overlapped, and there are often outliers that do not belong to the current cluster, resulting in unsatisfactory clustering results. Our model offers a new method to segment non-ideal data in overlapping regions. Since clustering algorithms cannot effectively identify and classify this part of the data, we split this part of the data and train it using a neural network. The results are then integrated into the clustered data. In the experiment, the k-fold cross-validation method ensures the model stability of the results. We used the accuracy to evaluate the quality of the model, and we used standard deviation and mean deviation to detect clustering results. Five sets of experimental data from the cross-experiment show that compared with the K-Means classification model, the accuracy of our model is effectively improved. Doi: 10.28991/HIJ-2024-05-03-012 Full Text: PDF

Abstract Immune checkpoint blockade therapy targeting the programmed death-1(PD-1) pathway has shown remarkable efficacy and durable response in patients with various cancer types. Early prediction of therapeutic efficacy is important for optimizing treatment plans and avoiding potential side effects. In this work, we developed an efficient machine learning prediction method using routine hematologic and biochemical parameters to predict the efficacy of PD-1 combination treatment in Pan-Cancer patients. A total of 431 patients with nasopharyngeal carcinoma, esophageal cancer and lung cancer who underwent PD-1 checkpoint inhibitor combination therapy were included in this study. Patients were divided into two groups: progressive disease (PD) and disease control (DC) groups. Hematologic and biochemical parameters were collected before and at the third week of PD-1 therapy. Six machine learning models were developed and trained to predict the efficacy of PD-1 combination therapy at 8–12 weeks. Analysis of 57 blood biomarkers before and after three weeks of PD-1 combination therapy through statistical analysis, heatmaps, and principal component analysis did not accurately predict treatment outcome. However, with machine learning models, both the AdaBoost classifier and GBDT demonstrated high levels of prediction efficiency, with clinically acceptable AUC values exceeding 0.7. The AdaBoost classifier exhibited the highest performance among the 6 machine learning models, with a sensitivity of 0.85 and a specificity of 0.79. Our study demonstrated the potential of machine learning to predict the efficacy of PD-1 combination therapy based on changes in hematologic and biochemical parameters.

Abstract 5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-β-galactosidase (SA-β-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

Abstract All types of ginger have common fundamental components, although they possess distinct strengths and inclinations when it comes to effectiveness and medicinal applications. Fresh ginger possesses the ability to effectively stimulate movement within the body, alleviate the act of vomiting, induce sweating, and provide relief for external syndromes. Dried ginger possesses both defensive and stimulant characteristics, which effectively raise the internal temperature and enhance the Yang energy. Fresh ginger is more hydrating than dried ginger, highly skilled at heating the Middle-jiao, alleviating pain, halting bleeding, and managing diarrhea. Dried ginger possesses the ability to alleviate coldness when consumed in a heated form, as well as to alleviate diarrhea when consumed in a heated form. It thrives in warm conditions and has a tendency to revert back to its warm nature. The moisture content of baked ginger is inferior to that of dried ginger, but it is highly effective in alleviating pain, bleeding, and diarrhea by warming the Middle-jiao. Ginger charcoal and stir-fried charcoal, produced through carbonization, have excellent heat retention properties and are effective in warming meridians and stopping bleeding. The potency and ability to spread of roasted ginger is less intense compared to fresh ginger, and its moisture content is not as low as that of dried ginger. The medicinal characteristics of this substance are gentle, making it beneficial for alleviating vomiting in patients who are physically frail. Its primary mode of action is on the Middle-jiao. Nevertheless, the main chemical compositions of various traditional Chinese medicines are nearly identical due to their shared base element. Ginger, in particular, possesses a range of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-bacterial, and anticoagulant properties. However, modern pharmacological research has not fully acknowledged the clinical medicinal value of ginger and consequently, fails to provide accurate guidance for clinical medication. This situation has a negative impact on the contemporary advancement of traditional Chinese medicine (TCM). The research on modernizing ginger is conducted by analyzing and considering the prospects. It is based on Traditional Chinese Medicine (TCM) theory and incorporates the comprehensive perspective of TCM philosophy. In order to modernize ginger, it is essential to have a proper knowledge of the concepts of “recognizing nature by efficacy, homology, and mutual expression of nature and efficacy” and “rationally utilizing modern drug research technology”. By applying these principles, we can construct a bridge towards the advancement of ginger.

Abstract The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.

【Objective】 Change in soil water content is not only an indicator of water stresses used for irrigation management but also controls biogeochemical processes in soil. In this paper, we study the feasibility of using thermal infrared imaging to estimate soil moisture dynamics. 【Method】 The experiment was conducted in July-August 2023 in a walnut orchard in Xinjiang. Thermal infrared images of the walnut canopy were measured continuously using a thermal infrared camera. Based on the HSV color space of the images, an improved K-means segmentation algorithm was proposed to analyze the change in canopy temperature. We also measured air temperature and humidity, illuminance, wind speed, atmospheric CO2, and soil water content in the 0-80 cm soil layer, from which we proposed an inversion model to estimate soil water dynamics. 【Result】 The improved K-means algorithm increased the accuracy from 82.34% to 94.55%, and the errors between the canopy temperature acquired from the images and the measured canopy temperature were in the range of 0 to 1.0. The infrared imaging method was most accurate between14:00 pm to 16:00 pm. Our results showed that the walnut roots were most active in taking up water from the 40-60 cm soil layer 50-60 cm away horizons from the tree truck. Canopy temperature, air temperature and relative humidity, and atmospheric CO2 concentration were correlated with soil water content at significant levels; they can thus be used to estimate soil water dynamics, with a coefficient of determination of R2=0.86 and p

Nano-zirconium carbide precursor was prepared by hydrothermal method. Nanometer zirconium carbide powder was prepared by carbothermal reduction reaction. The Gibbs free energy and enthalpy change of carbothermic reduction of zirconia were calculated by thermodynamic method. The reaction temperature and reaction mechanism of nanometer zirconia were calculated. The energy and phase changes during the reaction were studied by thermogravimetry and X-ray diffraction. Microstructure observation showed that the precursor was composed of multiple zirconia structures wrapped by a layer of amorphous carbon. This unique structure effectively prevents the agglomeration of the powder and ensures the dispersion of the prepared zirconia. This structure also ensures the dispersion of zirconium carbide powder. Zirconium carbide powder has uniform size and particle size of about 50 nm. Gibbs free energy calculation results show that when the temperature reaches 1656.56 °C, zirconia reacts with C to form CO and ZrC. As the temperature rises, ZrO2 reacts with CO to form CO2 and ZrC. The results of TG-DSC experiments show that the carbothermal reduction reaction starts at about 1100 °C and reaches its peak at 1418 °C. XRD analysis confirmed that ZrC appeared when the temperature reached 1450 °C, and the transformation was basically complete when the temperature exceeded 1600 °C.

IntroductionA critical issue in tropical forests is that anthropogenic deforestation (i.e., mining) degrades the integrity of its ecosystem. Reforestation with appropriate native plant species helps to alleviate these detrimental impacts. A protocol to select appropriate plant species for this purpose currently lacks efficacy and timeliness.MethodsWe provided a trait-based protocol to quickly and effectively select native plant species for mining reforestation. A 0.2-km2 area of Baopoling (BPL) at Hainan Island, China, was used as a study site, which has been severely degraded by 20 years of limestone mining for cement production. First, we identified the tree species in nearby undisturbed tropical forests, followed by evaluating the similarities in functional traits of the most dominant one (target species) and 60 local candidate native plant species (candidate species) whose saplings can be purchased from a local market.Results and discussionThis dataset was used in our trait-based protocol, and only within 1 month, we successfully selected eight plant species which are very similar to target species from the 60 candidate species. We also quantified whether the eight selected plant species were indeed suitable for sustained reforestation by testing their effects on landscape and also their survival rate and recruitment ability after using them to perform reforestation in BPL from 2016 to 2023. Finally, these eight plant species are indeed suitable for reforestation due to their huge influences on a significant shift from originally degraded landscape (comprising only barren rocks) to a forest landscape totally and also their high survival rate (90%–97%) and ability for natural recruitment after 7 years’ reforestation in BPL. Thus, we anticipate that this protocol would be integral to species selection during reforestation of tropical mining areas.

ObjectiveEpilepsy-related stigma is a global problem, yet there has been an inadequate focus on children and adolescents. The purpose of this study was to determine the status quo of stigma and its determinants among children and adolescents with epilepsy in China.MethodsA multicenter cross-sectional study was conducted across nine hospitals in eight cities within six provinces in China from 10 October 2023 to 15 June 2024. Participants included patients aged 8 to 18 years with epilepsy and their caregivers. Felt stigma was assessed with the Kilifi Stigma Scale for Epilepsy (KSSE). Social support and self-efficacy were collected through the Social Support Rating Scale (SSRS) and the Generalized Self-Efficacy Scale (GSES). The data were analyzed using t-tests, analysis of variance (ANOVA), Spearman correlation analysis, and multiple linear regression analysis.ResultsThe study enrolled 281 children and adolescents, with a mean age of 12.25 years (SD = 2.56), including 46.6% females. A total of 35.6% participants had self-reported felt stigma. The mean KSSE score is 9.58 (SD = 7.11). Meanwhile, stigma scores correlated strongly with reduced social support (r = −0.55, p 5 years), drug-resistant epilepsy (yes vs. no), comorbidities (yes vs. no), social support and self-efficacy are major influencing factors among the complex factors influencing the felt stigma among children and adolescents.ConclusionMedical staff should be more aware of stigma among children and adolescents with epilepsy, especially those who live in rural and western areas, have poor academic performance, have epilepsy duration of more than 5 years, have drug-resistant epilepsy, and have comorbidities, who are at higher risk of stigma. It is recommended that effective measures be taken to alleviate stigma by improving children and adolescents’ self-efficacy and providing more social support for them and their families.

Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients, difficult recruitment, long trial period, and frequent video interviews during the trial. Therefore, in the clinical operation of rare diseases, a decentralized clinical trials (DCT) model based on the " patient-centred" research and development concept is implemented. With the help of decentralized elements and digital health technology, the barriers of geographical restrictions can be overcome and subjects do not have to be limited to traditional clinical trial sites (hospitals/research centers), which can significantly reduce the burden on subjects, increase their representation, and obtain a wider range of scientific research data. To guide the industry′s scientific and standardized application of DCT in the research and development of drugs for rare diseases, the Center for Drug Evaluation of the National Medical Products Administration (NMPA) organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases. This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs. It aims to solve the difficult and key problems during rare disease drug research and development, improve the efficiency and optimize patient experience. This article, combining the research and development concepts in the guideline, explains the current research and development thinking on the application of DCT in the research and development of rare disease drugs, with a view of providing reference for the industry.

Abstract Background Aniridia is a rare eye disorder with a high incidence of glaucoma, and surgical intervention is often needed to control the intraocular pressure (IOP). Here, we reported a case of illuminated microcatheter-assisted circumferential trabeculotomy (MAT) performed on an aniridic glaucoma patient following a previous failed angle surgery. The surgical procedures for aniridic glaucoma were also reviewed. Case presentation A 21-year-old man, diagnosed with aniridic glaucoma, came to our hospital consulting for the poor control of left eye’s IOP despite receiving goniotomy surgery 3 years ago. The IOP was 26 mmHg with maximum topical antiglaucoma eyedrops. The central cornea was opaque and the majority of iris was absent. The gonioscopy and ultrasound biomicroscopy (UBM) demonstrated that 360° anterior chamber angle was closed. The whole exome sequencing of peripheral blood confirmed a 13.39 Mb copy number loss at chromosome 11p15.1p13, containing PAX6 and WT1 gene. The 360° MAT surgery was performed on his left eye. At 1-year follow-up, the IOP was 19mmHg with 2 kinds of topical antiglaucoma medications, and the postoperative UBM demonstrated the successful incision of the anterior chamber angle. Conclusions The case presented here exhibited a case of aniridic glaucoma treated by MAT surgery. The MAT surgery may be an effective option for IOP control in aniridic glaucoma patients following a previous failed angle surgery.

[Objective] The Loess Plateau is a great geographical unit of China, which has important strategic significance for national food security and ecological security. Through long-term slope management, comprehensive watershed management, afforestation and other measures, the ecological environment of the Loess Plateau has been significantly improved, but it still faces challenges in such aspects as insufficient rationality of vegetation restoration in local areas, uncoordinated overall planning of the whole basin, and balanced economic development and ecological protection. Under the guidance of the national dual-carbon goal, the future direction and goal of the Loess Plateau ecosystem and agricultural sustainable development should be to support the realization of carbon neutrality, establish an environmentally suitable vegetation community, promote the development of the ecosystem as a whole, and realize the green transformation of the development mode. [Methods] Based on the bibliometrics tool CiteSpace, this paper visually analyzes the relevant literatures on the principle and application of soil regulation in the Loess Plateau published from 1992 to 2023, focusing on the core research strength, research hotspot and research trend in this research field. [Results] (1) From the perspective of the evolution of the number of published papers, the overall trend is rising, and the growth rate is explosive after 2001; (2) From the perspective of publishing institutions, Northwest A&F University has the highest number of publishing institutions in this field, with 2 157; (3) From the perspective of the cooperative relationship between authors, Academician SHAO Mingan and Professor LIU Guobin are the core leaders in this field, and the number of published papers is 141 and 117 respectively. The cooperative network formed by them has been very mature; (4) From the perspective of research hotspots and development trends in this field, the main research hotspots focus on soil moisture, yield, dryland, soil erosion, soil nutrients and vegetation restoration, etc. The future micro theme trend will focus on yield, slope position and nitrogen application amount, while the future macro trend will explore a new model of the coupling and coordinated development of eco-economic-social system. [Conclusion] Based on the results of visual analysis, three perspectives on the principles and application of soil regulation in the Loess Plateau were proposed, including cooperative research, research hotspots and future key development directions.

Multi GPU systems achieve performance improvement through scaling out to meet the ever-increasing computation demand brought about by increasingly complex algorithms and the continuously increasing data in artificial intelligence. The interconnection bandwidth between processors, as well as topologies of systems are the key factors that determine the performance of multi-GPU systems. In traditional PCIe-based multi-GPU systems, the PCIe bandwidth is the bottleneck that limits system performance. GPU-oriented high speed interconnection technologies become an effective method to solve the bandwidth limitation problem of multi-GPU systems at present. This article first introduces the PCIe interconnection technology and the typical topologies used in traditional multi-GPU systems. Then taking Nvidia NVLink, AMD Infinity Fabric Link, Intel Xe Link, and Biren Technology BLink as examples, GPU-oriented high speed interconnection technologies and topologies of representative GPU vendors at home and abroad are reviewed and analyzed. Finally, the research implication of interconnection technologies is discussed.

In this study, we derive the Drazin inverse (A+εB)D{\left(A+\varepsilon B)}^{D} of the complex matrix A+εBA+\varepsilon B with Ind(A+εB)>1{\rm{Ind}}\left(A+\varepsilon B)\gt 1 and Ind(A)=k{\rm{Ind}}\left(A)=k and the group inverse (A+εB)#{\left(A+\varepsilon B)}^{\#} of the complex matrix A+εBA+\varepsilon B with Ind(A+εB)=1{\rm{Ind}}\left(A+\varepsilon B)=1 and Ind(A)=k{\rm{Ind}}\left(A)=k when εB\varepsilon B is viewed as the perturbation of AA. If the dual Drazin inverse (DDGI) A^DDGI{\widehat{A}}^{{\rm{DDGI}}} of A^\widehat{A} is considered as a notation. We calculate (A+εB)D−A^DDGI{\left(A+\varepsilon B)}^{D}-{\widehat{A}}^{{\rm{DDGI}}} and (A+εB)#−A^DDGI{\left(A+\varepsilon B)}^{\#}-{\widehat{A}}^{{\rm{DDGI}}} and obtain ‖(A+εB)D−A^DDGI‖P∈O(ε2)\Vert {\left(A+\varepsilon B)}^{D}-{\widehat{A}}^{{\rm{DDGI}}}{\Vert }_{P}\in {\mathcal{O}}\left({\varepsilon }^{2}) and ‖(A+εB)#−A^DDGI‖P∈O(ε2)\Vert {\left(A+\varepsilon B)}^{\#}-{\widehat{A}}^{{\rm{DDGI}}}{\Vert }_{P}\in {\mathcal{O}}\left({\varepsilon }^{2}). Meanwhile, we give some examples to verify these conclusions.

Constructing ecological security patterns (ESP) effectively maintains ecosystems' green, healthy, and sustainable development. The InVEST model and Conefor software were utilized in this study to pinpoint ecological sources (eco-sources) through a blend of landscape connectivity and the importance of ecosystem services (IES); the ecological resistance surface was constructed by synthesizing the gravity model and minimum cumulative resistance model (MCRM), extracted ecological corridors (eco-corridors) and nodes. Ultimately, the research in this study built the ESP for Xinjiang. The findings showed that: (1) 14 eco-sources were identified in Xinjiang, spanning an area of 2.13 × 105 km2; 32 eco-corridors were extracted, including 9 important and 23 general eco-corridors, comprising a total length of 1.26 × 104 km; identified 46 ecological nodes(eco-nodes); (2) the size of important and more important patches of ecosystem services in Xinjiang was 2.82 × 105 km2, which accounted for a relatively small size, and the value of ecosystem services was generally average. The overall level of landscape connectivity in the primary eco-sources was high, but the spatial distribution was uneven; (3) the ecological resistance values in Xinjiang vary significantly, with high-level resistance surfaces primarily located in the Junggar Basin and Tarim Basin and low-level resistance covering most of Xinjiang's natural ecological reserves and other areas. The study's findings can provide some references for constructing ESP at the provincial scale and in arid and semiarid regions and for planning spatial ecological restoration in Xinjiang.

Irrigated areas are major vectors of agricultural development and components of ecosystems. The groundwater level maintains the irrigated areas’ ecology safety and sustainable development. Under the influence of irrational irrigation practices—such as flood irrigation or extreme water saving without consideration of ecological impact—different areas within an irrigation district may experience anomalies in groundwater levels (either too deep or too shallow). It is of great significance to carry out research on water resource allocation and future water-saving strategies, taking into consideration groundwater depths. In this study, a method for the optimal allocation of irrigation water resources that considered groundwater level was used to regulate irrational irrigation practices and to reveal the future direction of water saving. Helan County in Ningxia province, an ecologically fragile and arid irrigated area, was selected as a case study. Multiple scenarios of different water use and different degrees of water-saving were analyzed. The results showed that non-engineering water-saving measures (such as adjusting the planting structure and controlling the amount of irrigation for rice) had better benefits compared to engineering measures (such as efficient water-saving irrigation and channel lining). When implementing only one water-saving measure, the strategy of replacing 75% of the rice area with corn yielded the best results. This approach can reduce the irrigation water shortage rate to 11% and increase by 4.58% the acreage where the groundwater level is reasonable. When multiple water-saving measures are implemented together, the most effective strategy for future water-saving efforts involves the joint implementation of several measures: replacing 75% of the rice area with corn, limiting irrigation for rice to no more than 11.85 thousand m3/ha, adopting high-efficiency water-saving irrigation in 90% of the pump-diverted water irrigation region and 40% of the channel-diverted water irrigation region, and maintaining the channel’s water utilization coefficient at 0.62. This strategy can keep the irrigation water shortage below 3.66% and increase the acreage where the groundwater level is reasonable, by 4.58% per year. The conclusions and research approaches can provide references for the formulation of water-saving measures for irrigated areas’ sustainable development.

This paper first introduces the architecture of the natural language processing system and then analyzes how natural language processing decomposes the probability distribution function by multi-factor form and Bayesian formula to improve the efficiency of function description. Then, NLM is applied to enhance the statistical coefficients of the N-gram model, which solves the problems of data sparsity and dimensionality disaster. By using natural language understanding in English teaching practice and experimenting with the teaching effect, it was found that the overall English achievement of the experimental group increased by 5.4 points, the average Z-score reached more than 3 points, and 96.6% of the students were interested in the teaching method. The new teaching method is demonstrated to have a significant impact on the improvement of English scores.

Background: Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice. Objective: We performed a systematic review and meta-analysis on the use of QSM in MS. Methods: Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively. Results: After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39–0.70, I2 = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19–0.57, I2 = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28–0.67, I2 = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = −0.39, 95 % CI = −0.66–−0.12, I2 = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16–0.53, I2 = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions. Conclusions: We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.

To solve the problem of the lack of effective algorithmic models to improve the accuracy of lexical disambiguation in English translation, this paper constructs a twin network lexical disambiguation model based on the characteristics of twin networks, and studies the construction process from the original corpus to the input sample pairs. The Stacked-LSTM algorithm is utilized to align the input Chinese and English corpus and expand the dataset. To achieve disambiguation, the input sample similarity is calculated after training the twin neural network, which extracts corpus features using BiLSTM Attention. After comparing the disambiguation experiments of various algorithms, the model of this algorithm can effectively calculate the similarity of the input samples and achieve the disambiguation accuracy of 68.23% for English vocabulary translation, and 87.0% for vocabulary segmentation of complex English sentences or articles. This shows that the model of this algorithm has good performance for disambiguating English translations.

The use of an initial state value function and an optimal strategy are used in this paper to solve educational problems based on deep reinforcement learning. Deep reinforcement learning’s approximate function is defined, and the matrix model is created by training tuning using learning methods like gradient descent. To analyze the modeling process of reinforcement learning, reward values are added to the Markov decision transfer matrix and the expected value of cumulative returns is calculated. The weights are trained using the Bellman equation to enhance the algorithm’s stability. In evaluating the effect of reform and innovation in Civic Education, the teacher education concept is rated as 10 points. The reform and innovation of civic education, combined with deep reinforcement learning, can promote the reform of education and teaching modes, improving the efficiency and quality of education.

ObjectiveTo explore the chain-mediated role of sense of career benefit and sense of career mission in the mechanism of psychological flexibility’s effect on nurses’ work engagement.MethodsAdopting the convenience sampling method, 1032 nurses in 10 general hospitals in Sichuan Province were surveyed by questionnaires using the General Information Questionnaire, Sense of Occupational Benefit Scale, Sense of Occupational Mission Scale, Psychological Flexibility Scale, and work engagement Scale in August-October 2022, and the model of the chained-mediated effect was constructed and validated.ResultsThe total psychological resilience score of nurses in 10 general hospitals in Sichuan Province was (91.29 ± 17.38), the total score of sense of occupational benefit was (137.85 ± 21.02), the total score of sense of occupational mission was (40.27 ± 7.37), and the total score of work engagement was (34.99 ± 9.80). The total score of nurses’ work engagement was positively correlated with the total scores of psychological elasticity, sense of professional benefit, and sense of professional mission (all P < 0.05). The direct effect of psychological elasticity on nurses’ work engagement was significant, with an effect value of 0.321; the chain mediation effects of occupational benefit and occupational mission as separate mediators and the chain mediation effects of the two were 0.039, 0.032, and 0.062, respectively.ConclusionNurses’ work engagement in 10 general hospitals in Sichuan province is at a medium level, and occupational benefit and occupational mission play a significant role in the mechanism of the psychological elasticity’s effects on nurses’ work commitment, and the chain mediation effect of occupational mission in the mechanism of psychological elasticity is established. The chain mediation effect in the mechanism was established. Managers should pay attention to nurses with low psychological elasticity, improve their sense of occupational benefit, and enhance their sense of occupational mission in order to further promote the enhancement of work engagement.

Salinization is one of the significant factors that impede agricultural development, threaten ecological security, and hinder sustainable development. This study successfully achieved precise and expeditious identification of salinization grades by integrating optical satellite data with other geospatial information. It effectively enhanced the accuracy of salinization inversion, with a recognition rate of 85.34%. The salinization in the Hexi irrigation area showed a decreasing trend from 2014 to 2023, with no and slight salinization increasing by 8.37% and 3.54%, while moderate and severe salinization decreased by 17.23% and 19.11%. This was mainly due to changes in hydrological processes, shown by a 5.6% and 6.8% decrease in water diversion and drainage, and a roughly 0.45 m rise in groundwater depth. Through the analysis of the relationship between salinization and groundwater depth, it is found that the further north the area is, the more severe the salinization. And the shallower the groundwater depth, the more difficult it is to maintain the groundwater depth at the threshold to prevent salinization. It is primarily due to obstructed drainage in the northern region, leading to salinization. Through exploring the reasons for drainage obstruction, the causes of salinization in different regions were identified. This research aims to provide some reference for the investigation, regulation, and management of regional salinization.

Background: Although transradial access (TRA) has become the main vascular access for coronary intervention, its high radial artery occlusion rate limits its application in some patients. Studies have shown that compared with TRA, distal transradial access (dTRA) with the snuffbox area or the Hegu acupoint area as the puncture point significantly decreases the incidence of radial artery occlusion. However, no randomized controlled study has confirmed the safety and efficacy of coronary artery intervention via dTRA in China. Methods and analyses: This single-center, prospective, randomized controlled, superiority open-label study will enroll 428 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention as the study population. After preoperative evaluation, the participants will be randomly divided into a study group (dTRA) and control group (TRA) in a 1:1 ratio. The primary endpoint (radial artery occlusion at 24 hours after operation) and secondary endpoint events will be evaluated and recorded. Study registration: This study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300073902).

Buildings are, collectively, a high-energy-consuming sector, accounting for as much as 50.9% of total carbon emissions. With the introduction of carbon peaks and neutrality as carbon reduction strategies, carbon emissions reduction has become a research hotspot in the construction industry. Most of the current research focuses on residential and public buildings; the carbon footprint of industrial buildings has been less explored. In this study, we focused on a subset of industrial buildings, the energy substations in Xiamen, China. The carbon intensity of the three stages of material production, transportation, and operation is calcu-lated. The results of the study show that the three stages of whole-life cycle carbon emissions are 1,612,889.25, 51,038.9 and 17,034,352.5 kgCO2e, and the percent are 8.63%, 0.27% and 91.10%, respectively.

Water conservation is imperative for alleviating water shortages and fostering the establishment of a water-saving society. However, the implementation of water-saving measures caused an increase in the depth to groundwater, resulting in ecological issues. Therefore, reasonable water saving should consider the appropriate depth to groundwater and its evolution trend. This study focuses on the Helan irrigation area in Ningxia as the research subject, aiming to establish thresholds for agricultural water-saving measures while considering constraints by depth to groundwater. The evolution trend of depth to groundwater from 1995 to 2018 was analyzed using the k-Shape cluster and complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) methods. Then, the thresholds of agricultural water-saving measures involved comparing groundwater numerical simulation results for water-saving scenarios, with the control area of ecological groundwater table depth and water shortage rate serving as the evaluation indices. The thresholds for implementing agricultural water-saving measures are as follows: the canal water utilization coefficient is set at 0.62; the proportion of water-efficient irrigation areas to effective irrigation areas should be 40% in the Yellow River irrigation area and 90% in the pumps-up Yellow River irrigation area; additionally, a reduction of 75% in the rice planting area is targeted.

Molecular oxygen redox electrocatalysis involves oxygen reduction and evolution as core reactions in various energy conversion and environmental technology fields. Strong metal-support interactions (SMSIs) based nanomaterials are regarded as desirable and state-of-the-art heterogeneous electrocatalysts due to their exceptional physicochemical properties. Over the past decades, considerable advancements in theory and experiment have been achieved in related studies, especially in modulating the electronic structure and geometrical configuration of SMSIs to enable activity, selectivity, and stability. In this focuses on the concept of SMSI, explore their various manifestations and mechanisms of action, and summarizes recent advances in SMSIs for efficient energy conversion in oxygen redox electrocatalysis applications. Additionally, the correlation between the physicochemical properties of different metals and supports is systematically elucidated, and the potential mechanisms of the structure-activity relationships between SMSIs and catalytic performance are outlined through theoretical models. Finally, the obstacles confronting this burgeoning field are comprehensively concluded, targeted recommendations and coping strategies are proposed, and future research perspectives are outlined., (© 2024 Wiley‐VCH GmbH.)

Nitrogen (N) fertilizer application ensures crop production and food security worldwide. N-controlled boosting of shoot branching that is also referred as tillering can improve planting density for increasing grain yield of cereals. Here, we report that Sugar Transporter Protein 28 (OsSTP28) as a key regulator of N-responsive tillering and yield formation in rice. N supply inhibits the expression of OsSTP28, resulting in glucose accumulation in the apoplast of tiller buds, which in turn suppresses the expression of a transcriptional inhibitor ORYZA SATIVA HOMEOBOX 15 (OSH15) via an epigenetic mechanism to activate gibberellin 2-oxidases (GA2oxs)-facilitated gibberellin catabolism in shoot base. Thereby, OsSTP28-OSH15-GA2oxs module reduces the level of bioactive gibberellin in shoot base upon increased N supply, and consequently promotes tillering and grain yield. Moreover, we identify an elite allele of OsSTP28 that can effectively promote N-responsive tillering and yield formation, thus representing a valuable breeding target of N use efficiency improvement for agricultural sustainability., (© 2024. The Author(s).)

Herein, we report a novel strategy of hypervalent iodine(III) compound-mediated selective C sp -C sp bond cleavage of alkynes and C═N/N-O bond cleavage of nitrones and recombination of C-C/C-O/C-N multiple bonds to access various functionalized [1,4]oxazinones bearing a vicinal carbon stereocenter in good yields and high diastereoselectivity. Mechanistic studies revealed that the reaction undergoes a domino [4 + 3] cycloaddition, 1,3-rearrangement of N-O bond, intramolecular cyclization, dearomatization, and rearomatization over four steps in a single flask. The present method features good functional group tolerance, broad substrate scope, and C-C/C═N/N-O multiple bonds cleavage and recombination.2 bond cleavage of alkynes and C═N/N-O bond cleavage of nitrones and recombination of C-C/C-O/C-N multiple bonds to access various functionalized [1,4]oxazinones bearing a vicinal carbon stereocenter in good yields and high diastereoselectivity. Mechanistic studies revealed that the reaction undergoes a domino [4 + 3] cycloaddition, 1,3-rearrangement of N-O bond, intramolecular cyclization, dearomatization, and rearomatization over four steps in a single flask. The present method features good functional group tolerance, broad substrate scope, and C-C/C═N/N-O multiple bonds cleavage and recombination.

Pain emotion is a negative emotion caused by pain, which seriously affects the patients' physical and psychological health. The anterior cingulate cortex (ACC) is a key brain region in the occurrence and regulation of pain and painful emotion. In this paper, we summed up the relevant progress of researches on acupuncture improvement of pain emotion from neurotransmitters and receptors, cellular signaling pathways and neural circuits of ACC, in order to provide a basis for further research. 1) Acupuncture can regulate the long-term potentiation of ACC synaptic transmission by down-regulating the expression of N-methyl-D-aspartic acid receptor (NMDAR)； and up-regulating the expression of μ-, delta- and κ-opioid receptors, neuropeptide S (NPS)/ NPS receptor, and the number of parvalbumin-expressing interneurons to reduce neuronal excitability, relieving pain emotion； 2) Acupuncture can regulate synaptic transmission of ACC neurons by inhibiting protein kinase Mζ (PKMζ)-GluR1 and cAMP/PKA-ERK-CREB signaling pathways, and modulate synaptic plasticity to ameliorate pain emotion； 3) Acupuncture intervention induced inhibition of rostral ACC Glu -thalamic circuit may result in relief of pain emotion but not pain sensation, whereas inhibition of the rostral ACC Glu -ventrolateral periaqueductal gray matter(vlPAG) circuit may relieve pain sensation but not pain emotion. In addition, our team found that in the treatment of painful diseases by acupuncture, the addition of "spirit-regulating" acupoints can not only improve patients' negative emotion, but also significantly relive patients' pain sensation.

The employment policies targeted at university graduates, which are exceedingly valuable to the national human resource, are closely related to the national economy and people's livelihood. The employment policies for college students are essential pathways for promoting high-quality job placement for graduates, making the review and evaluation of relevant policies exceedingly significant. This study analyzes the university-student employment policies issued between 1997 and 2023; the researchers utilize text mining and content analysis and refer to the policy indicators designed by existing scholars to develop an evaluation index for college student employment. A PMC index model was constructed to quantitatively evaluate 9 selected policy samples. The results indicate that P5, P6, and P7 have good consistency ratings; P8, P4, and P9 have acceptable consistency ratings; and P2, P3, and P1 have low consistency ratings. The average score for the 9 policy samples is 5.03, reflecting an overall satisfactory quality of China's college student employment policies. By constructing a PMC surface, the model visually reveals certain deficiencies in China's college-student employment policies in regard to policy design, policy tools, and policy content. This study provides countermeasures and proposals from aspects such as policy nature and policy measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cui, Wang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hyperuricemia (HUA) and gout have been demonstrated as independent risk factors for cardiovascular disease. The relationship between the recently updated Life's Essentials 8 (LE8), which measures ideal cardiovascular health (CVH), and HUA and gout remains unclear. The aim of this study was to explore the relationship between CVH and the prevalence of HUA and gout among a nationally representative sample of US adults., Methods: This study utilized cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) for the years 2007 to 2018. The CVH scores and their corresponding components were defined according to the guidelines established by the American Heart Association. The association between the LE8 score and both HUA and gout was assessed using weighted multivariable logistic and restricted cubic spline (RCS) models., Results: Among the 21,155 participants aged 20 years and older, the prevalence of HUA was 17.20% (95% CI, 16.05-18.36%), and the prevalence of gout was 3.58% (95% CI, 3.13-4.02%). After adjusting for potential confounders, compared to participants exhibiting low CVH, the multivariable adjusted odds ratio (OR) for HUA was 0.65 (95% CI, 0.56-0.75) in those with moderate CVH, and 0.25 (95% CI, 0.20-0.31) in those with high CVH. Additionally, compared to participants with low CVH, the multivariable adjusted OR for gout was 0.66 (95% CI, 0.53-0.81) in those with moderate CVH and 0.32 (95% CI, 0.20-0.50) in those with high CVH. The LE8 score exhibited a significant nonlinear negative association with HUA and linear negative correlation with gout. In subgroup analyses focusing on HUA, significant interactions were observed between LE8 score and age, sex, and CKD (P for interaction < 0.05). For gout, only a significant interaction between LE8 score and sex was observed (P for interaction < 0.05)., Conclusions: Among adults, there was a significant negative correlation between LE8 score and the prevalence of HUA and gout. Maintaining an ideal CVH may be beneficial in reducing the burden of HUA and gout., (© 2024. The Author(s).)

Theranostics, by integrating diagnosis and therapy on a single platform, enables real-time monitoring of tumors during treatment. To improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic imaging modalities can complement each other to achieve high resolution and a deep penetration depth. Despite the superior performance, the biodegradability of theranostic agents plays a critical role in enhancing nanoparticle excretion and reducing chronic toxicity, which is essential for clinical applications. Herein, we synthesize biocompatible and biodegradable indocyanine green (ICG)-conjugated germanium nanoparticles (GeNPs) and investigate their biodistributions in nude mice and 4T1 tumor models after intravenous injections using near-infrared (NIR) dual-modality fluorescence and photoacoustic imaging. The ICG-conjugated GeNPs have strong NIR absorption due to the NIR-absorbing ICG and Ge in combination, emit strong NIR fluorescence due to the multilayered ICG coatings, and exhibit very low in vitro and in vivo toxicity. After tail vein injections, the ICG-conjugated GeNPs mainly accumulate in the liver and spleen as well as the tumor with the help of the enhanced permeability and retention effect. The tumor's fluorescence signal is much stronger than that of the control group injected with pure ICG solution, as the GeNPs can function as biodegradable carriers for efficiently delivering the ICG molecules to the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the tumor can also be utilized for photothermal treatment under NIR laser irradiation, after which the tumor volume almost diminishes after 14 days. The experimental findings in this work demonstrate that the ICG-conjugated GeNPs are promising theranostic agents with exceptional biodegradability for in vivo NIR dual-modality imaging and photothermal therapy.

Oral corticosteroids represents the most prevalent treatment for idiopathic granulomatous mastitis. Ductal lavage with triamcinolone acetonide and antibiotics followed by observation (DL-OBS) has emerged as a novel strategy, but a comparison of them remains lacking. Here in this multicenter, open-label, non-inferiority, randomized trial (ClinicalTrials.gov identifier: NCT03724903), we assigned 140 patients to oral corticosteroids (N = 71) and DL-OBS (N = 69), stratified by baseline M-score. The primary outcome is complete Clinical Response rate at 1 year. The non-inferiority margin is -15%. The primary outcome is 85.5% in DL-OBS and 87.3% in oral corticosteroids (difference: -1.8%; 95%CI, 13.2 to 9.5; P non-inferiority  = .01) in intention-to-treat population, and 92.6% vs 98.2% (difference -5.6%; 95%CI -13.4 to 2.2; P non-inferiority  = .01) in per-protocol population, respectively. The most common (>15%) adverse events were Cushingoid, epigastric pain and arthralgia in oral corticosteroids, and irregular menstruation in DL-OBS, respectively. Here, we report that DL-OBS shows similar efficacy to oral corticosteroids but with better safety profile., (© 2024. The Author(s).)

Near-neutral HCO 3 - aqueous solution plays an essential role in respiratory, mineralization and catalysis, yet the interconversion between hydrated CO 2 , HCO 3 - and CO 3 2- and the associated proton transfer under such proton-deficient conditions remain uncovered. Here we reveal that cation enables HCO 3 - to self-dissociate into OH - and CO 2 through a pH-independent process, where CO 2 hydration and subsequent proton transfer in acid-base reactions lead to the overall exchange of oxygen isotopes between HCO 3 - and H 2 O tracked by oxygen isotope-labeled Raman spectroscopy. Isolating HCO 3 - from cations with crown ether impedes HCO 3 - dissociation and the following reactions. Further molecular dynamics simulations demonstrate that the interplay between HCO 3 - and hydrated cations drives HCO 3 - dissociation. This study suggests a natural proton channel upon coupling HCO 3 - with cations., (© 2024. The Author(s).)

Diabetic limb ischemia (DLI) is a frequent complication of diabetes and the leading cause of non-traumatic amputation. Traditional treatments like stent placement and bypass surgery may not suit all patients. Exosome transplantation has emerged as a promising therapy. Netrin1, a protective cardiovascular factor, has an unclear role in DLI. This study investigates the role of Netrin1 in DLI patients and evaluates the therapeutic potential of exosomes derived from Netrin1-overexpressing adipose-derived stem cells (N-ADSCs). The expression of Netrin1 is significantly decreased in both endothelial cells and serum of DLI patients, highlighting its potential as a biomarker or therapeutic target. In vitro, Netrin1-enriched exosomes (N-Exos) promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation, and increased resistance to apoptosis under high glucose conditions. These protective effects are mediated through PI3K/AKT/eNOS and MEK/ERK pathways, and N-Exos further facilitated macrophage polarization from M1 to M2. In vivo, N-Exos demonstrates superior therapeutic effects over ADSC exosomes (Exos), including enhanced angiogenesis, improved collateral artery remodeling, reduced inflammation, and muscle protection. Collectively, these findings identify Netrin1 as a critical factor in DLI and underscore its significance in disease progression and therapeutic strategies. N-Exos offers a promising non-cellular therapeutic approach for the treatment of DLI., (© 2024 Wiley‐VCH GmbH.)

Background: Hepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis., Methods: We constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I-IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes., Findings: As the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)