Tuning Octahedron Sites of CoV2O4 via Cationic Competition for Efficient Oxygen Evolution Reaction.

Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.

Breast Cancer With HER2 Immunohistochemical Score 2 and Average HER2 Signals/Cell 6 or More and HER2/CEP17 Ratio Less Than 2 ('ISH Group 3'): A Multiinstitutional Cohort Analysis Emphasizing Outcome and Molecular Subtype.

Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio <2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay. Although such patients are currently eligible for treatment with HER2-targeted therapy, their characteristics and outcomes remain poorly understood. Sixty-two BCs with equivocal HER2 immunohistochemical score (2+) and reflex ISH group 3 results were identified across 4 institutions. Available clinicopathologic characteristics, MammaPrint and BluePrint molecular results, and follow-up information were retrospectively analyzed. Most BCs with HER2 equivocal immunohistochemical and ISH group 3 results were histologic grade 2 or 3 (100%), estrogen receptor (ER) positive (90.3%), with an average HER2 signals/cell of 7.3. Molecular profiles revealed that 80% (16/20) of tumors were luminal subtypes, and HER2 molecular subtype was identified in 10% of tumors (2/20). Twelve (19.4%) out of 62 patients developed local recurrence and/or distant metastasis with a median follow-up of 50 months. One (10%) of 10 patients achieved pathologic complete response after neoadjuvant chemotherapy. Forty-nine (79%) out of 62 patients completed anti-HER2 agents, and exploratory analysis showed no statistically significant difference in disease outcomes between patients who completed anti-HER2 treatment and those who did not. Univariate analysis revealed advanced clinical stage, and ER/progesterone receptor negativity was associated with unfavorable disease outcomes, and exploratory multivariate analysis demonstrated that clinical stage was the most significant factor associated with disease outcomes in the studied population. These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

PURPOSE: In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. METHODS: Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. RESULTS: Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2- to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2- (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). CONCLUSION: Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Rosai-Dorfman disease manifesting as a solitary mass with fat in the thymus a case report.

BACKGROUND: Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare, self-limiting disease that predominantly affects children and young adults. Moreover, the disease is characterized by painless bilateral cervical lymphadenopathy in 95% of the patients. However, few reports are available on the Rosai-Dorfman disease of the thymus. CASE PRESENTATION: We report a rare case of thymic Rosai-Dorfman disease detected using computed tomography. During a medical examination, a 50-year-old man underwent a chest computed tomography scan, which revealed an anterior mediastinal single mass with fat in the thymus. A thymectomy was performed to completely remove the tumor using a thoracoscopic technique due to a clinical suspicion of thymoma. Furthermore, Rosai-Dorfman disease was confirmed using histological and immunohistochemical analyses. CONCLUSIONS: To the best of our knowledge, this is the sixth case of thymus-affecting solitary Rosai-Dorfman disease with histological and immunohistochemical evidence. Fat in the thymus, as was present in this case, has never been described in Rosai-Dorfman disease previously. Our results highlight the challenge of diagnosing this uncommon tumor before surgery, and more cases need to be reported to help with the preoperative diagnosis of such a rare tumor.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

T2WI-based MRI radiomics for the prediction of preoperative extranodal extension and prognosis in resectable rectal cancer.

OBJECTIVE: To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer. METHODS: One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS). RESULTS: Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233-5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247-5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710). CONCLUSION: The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS. CRITICAL RELEVANCE STATEMENT: A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer. KEY POINTS: • Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS.

Preconditioning exercise reduces brain damage of ischemic stroke in rats via PI3K-AKT pathway by bioinformatic analysis.

Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.

Enriched environment enhanced the astrocyte-derived BDNF and VEGF expression and alleviate white matter injuries of rats with ischemic stroke.

OBJECTIVES: Numerous studies have shown that an enriched environment can promote ischemic stroke and improve cognitive function. In addition, white matter is closely related to cognitive function. The effects and mechanisms of the enriched environment on white matter recovery after stroke have not been elucidated. This study will analyse the effects of the enriched environment on white matter and cognitive function in the post-stroke brain from the perspective of astrocytes and their secretions. METHODS: Stroke models were used for middle cerebral artery occlusion model. post-operative rats were divided into sham-operated, standard and enriched environment groups. The degree of cerebral infarction was assessed by TTC staining and the degree of white matter damage was assessed by Luxol-Fast Blue staining. The prognosis after stroke was assessed using the longa score and Morris water maze test. Western Blot and immunofluorescence were used to quantify and localize astrocytes and their associated secretory factors and myelin protein markers. RESULTS: We found that ischemic stroke can cause severe demyelination. After EE treatment, there was a significant increase in cerebral remyelination and a significant improvement in neurological and cognitive functions. Astrocyte, BDNF, and VEGF expression were significantly higher than in rats in the standard circumstances of stroke model. CONCLUSION: These data suggest that the enriched environment contributes to brain white matter recovery and improvement of cognitive function after stroke. The mechanism is related to astrocytes and their secretions. EE can activate astrocytes to secrete BDNF and VEGF, which may be crucial to promote white matter recovery.

Insight into the role of non-coding RNA in the diagnosis and treatment of retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy. The course of RP is irreversible and leads to progressive loss of vision. It is characterized by hypotrophic degeneration of photoreceptor cells and retinal pigment epithelium. Multiple factors are involved in the development of the disease, including apoptosis, oxidative stress, and inflammatory/immune responses. In the past decades, gene therapy, stem cell therapy and other therapeutic approaches have been extensively investigated. However, due to the heritability and high heterogeneity of the disease and the difficulty in diagnosis and treatment, there is still a lack of standardized and effective therapies. Therefore, there is a need to develop new diagnostic and therapeutic approaches suitable for diseases with pathogenic mutations. With the understanding of the interaction between gene expression regulation and retinal pathology, the value of clinical applications of non-coding RNAs (ncRNAs) in retinal degeneration has gained attention. There is growing evidence that ncRNAs are widely distributed and involved in the regulation of multiple biological processes in the retina as well as processes associated with the development of RP, making them promising biomarkers for the diagnosis, treatment, and prognosis of RP. This paper reviews the crosstalk between ncRNA and RP, systematically discusses the role of ncRNAs in normal retinal cell physiology and RP pathogenesis and explores the potential of ncRNAs as therapeutic agents for clinical applications in RP.

Functions of metal-phenolic networks and polyphenol derivatives in photo(electro)catalysis.

Phenolic compounds are ubiquitous in nature because of their unique physical and chemical properties and wide applications, which have received extensive research attention. Phenolic compounds represented by tannic acid (TA) play an important role at the nanoscale. TA with a polyphenol hydroxyl structure can chemically react with organic or inorganic materials, among which metal-phenolic networks (MPNs) formed by coordination with metal ions and polyphenol derivatives formed by interactions with organic matter, exhibit specific properties and functions, and play key roles in photo(electro)catalysis. In this paper, we first introduce the fundamental properties of TA, then summarize the factors influencing the properties of MPNs and structural transformation of polyphenol-derived materials. Subsequently, the functions of MPNs and polyphenol derivatives in photo(electro)catalysis reactions are summarized, encompassing improving interfacial charge carrier separation, accelerating surface reaction kinetics, and enhancing light absorption. Finally, this article provides a comprehensive overview of the challenges and outlook associated with MPNs. Additionally, it presents novel insights into their stability, mechanistic analysis, synthesis, and applications in photo(electro)catalysis.

Experiences of decisional conflict related to epidural labour analgesia among women during late pregnancy in a tertiary hospital in China: a mixed methods study.

BACKGROUND: Research has indicated some women were in a state of uncertainty about pharmacological pain management decisions, which may lead to maternal anxiety and decisional regret. However, little is known about decisional conflict in the choice of epidural labour analgesia amongst Chinese women. AIM: This study aimed to investigate the level of and reasons underlying decisional conflict in Chinese women during their late pregnancy when making a decision on the use of epidural analgesia in labour. METHODS: A convergent parallel mixed methods study was undertaken, that included a quantitative survey (n = 323) and qualitative interviews (n = 17) with women recruited from a tertiary general hospital in Hangzhou, China. The quantitative survey assessed the level of and its influencing factors of women's decisional conflict, while the qualitative interview further explored experiences of and reasons underlying the conflict. FINDINGS: Participants reported a high level of decisional conflict (mean±SD, 39.59±15.92), which related to decision delay and/or negative perceptions about the decision. Multiple stepwise linear regression analysis identified that highest level of education and knowledge of epidural were negatively associated with decisional conflict (p<0.05). Four decision-making styles (rational, dependant, intuitive and avoidant decision-making) associated with different levels of decisional conflict, and four underlying reasons (personal characteristics, informational provision, emotional support and participation in decision-making) of the conflict were thematized. CONCLUSION: Decisional conflict related to epidural labour analgesia is a noteworthy issue amongst women during their late pregnancy. This study suggests a need for provision of family-centred shared decision-making practice about the use of epidural analgesia in labour.

Recent Advances in the Preparation and Application of Two-Dimensional Nanomaterials.

Two-dimensional nanomaterials (2D NMs), consisting of atoms or a near-atomic thickness with infinite transverse dimensions, possess unique structures, excellent physical properties, and tunable surface chemistry. They exhibit significant potential for development in the fields of sensing, renewable energy, and catalysis. This paper presents a comprehensive overview of the latest research findings on the preparation and application of 2D NMs. First, the article introduces the common synthesis methods of 2D NMs from both "top-down" and "bottom-up" perspectives, including mechanical exfoliation, ultrasonic-assisted liquid-phase exfoliation, ion intercalation, chemical vapor deposition, and hydrothermal techniques. In terms of the applications of 2D NMs, this study focuses on their potential in gas sensing, lithium-ion batteries, photodetection, electromagnetic wave absorption, photocatalysis, and electrocatalysis. Additionally, based on existing research, the article looks forward to the future development trends and possible challenges of 2D NMs. The significance of this work lies in its systematic summary of the recent advancements in the preparation methods and applications of 2D NMs.

Recent advances in the study of circadian rhythm disorders that induce diabetic retinopathy.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes mellitus and a major cause of blindness in young adults. Multiple potential factors influence DR; however, the exact mechanisms are poorly understood. Advanced treatments for DR, including laser therapy, vitrectomy, and intraocular drug injections, slow the disease's progression but fail to cure or reverse visual impairment. Therefore, additional effective methods to prevent and treat DR are required. The biological clock plays a crucial role in maintaining balance in the circadian rhythm of the body. Poor lifestyle habits, such as irregular routines and high-fat diets, may disrupt central and limbic circadian rhythms. Disrupted circadian rhythms can result in altered glucose metabolism and obesity. Misaligned central and peripheral clocks lead to a disorder of the rhythm of glucose metabolism, and chronically high sugar levels lead to the development of DR. We observed a disturbance in clock function in patients with diabetes, and a misaligned clock could accelerate the development of DR. In the current study, we examine the relationship between circadian rhythm disorders, diabetes, and DR. We conclude that: 1) abnormal function of the central clock and peripheral clock leads to abnormal glucose metabolism, further causing DR and 2) diabetes causes abnormal circadian rhythms, further exacerbating DR. Thus, our study presents new insights into the prevention and treatment of DR.

Recent advances in MXene-based nanocomposites for supercapacitors.

MXene materials have become a competitive candidate for electrochemical energy storage due to their unique two-dimensional layered structure, high density, metal-like conductivity, fast ion intercalation, tunable surface terminal groups, and good mechanical flexibilities, showing unique application advantages in the field of supercapacitors. With widely research of MXene in energy storage applications, plenty of studies in synthesis strategies of MXene, including etching, intercalation and exfoliation processes, and its charge storage mechanism in supercapacitors have been conducted. However, the restacking of two-dimensional MXene nanosheets severely affects their electrochemical performance. To prevent the stacking of MXene, MXene-based nanocomposite electrode materials have been developed with remarkable electrochemical performance by incorporating conventional active capacitive materials, including metal oxides/sulfides and conductive polymers, with MXene. This review summarizes the etching strategies of MXenes and selection of intercalants, also discusses the charge storage mechanism of MXenes in aqueous and nonaqueous electrolytes. It mainly expounds the preparation strategies and applications of MXene-based nanocomposites in supercapacitors, including MXene/metal oxide, MXene/metal sulfide, MXene/conducting polymer, and MXene/carbon-based composites. Additionally, the advantages of combining MXene with other active materials in supercapacitor applications, which support its promising prospects, are discussed. Finally, the critical challenges faced by MXene-based nanocomposites in long-term research are mentioned.

[Regularity of meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea and secondary dysmenorrhea patients].

OBJECTIVE: To observe the meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea(PD) and secondary dysmenorrhea(SD) patients, so as to summarize the rules of meridian-acupoint reaction and acupoints selection. METHODS: Thirty-five patients with PD (PD group), 34 patients with SD (SD group) and 35 healthy subjects (healthy group) were recruited. The compression method was used to examine the lower leg segment of the foot three yin meridians. Positive reactions(palpable skin changes, including cords, nodules, depressions) and tenderness of meridians and acupoints were recorded. The visual analogue scale (VAS) was used to evaluate the tenderness severity of acupoints. RESULTS: Compared with the healthy group, the probability of positive reactions and tenderness in foot three yin meridians were higher in PD and SD groups (P<0.01,P<0.05). Compared with the PD group, the probability of positive reactions in Spleen and Liver Meridians were higher in the SD group, with higher probability of tenderness in Liver Meridian(P<0.05). The probability of positive reactions and tenderness in the Spleen Meridian of PD and SD groups was significantly higher than that in the Kidney Meridian (P<0.01), while the probability of tenderness in the Spleen Meridian of the PD group was significantly higher than that in the Liver Meridian (P<0.05). Positive reactions and tenderness were concentrated at Yinlingquan (SP9), Diji (SP8) and Sanyinjiao (SP6) of Spleen Meridian and Xiguan (LR7) and Ligou (LR5) in Liver Meridian of PD and SD groups. In comparison with the PD group, the probability of positive reactions, tenderness and VAS score of SP8 and LR5 of the SD group were higher (P<0.05, P<0.01). CONCLUSION: The positive reaction occurs most frequently in the Spleen Meridian, followed by the Liver Meridian, and least frequently in the Kidney Meridian. The acupoints with positive reaction are different between PD and SD, which suggests that the Spleen Meridian acupoints should be the main acupoints when treating the two kinds of dysmenorrhea, and acupoints should also be selected according to the meridian and acupoint examination results.

MRI-based multiregional radiomics for preoperative prediction of tumor deposit and prognosis in resectable rectal cancer: a bicenter study.

OBJECTIVE: To build T2WI-based multiregional radiomics for predicting tumor deposit (TD) and prognosis in patients with resectable rectal cancer. MATERIALS AND METHODS: A total of 208 patients with pathologically confirmed rectal cancer from two hospitals were prospectively enrolled. Intra- and peritumoral features were extracted separately from T2WI images and the least absolute shrinkage and selection operator was used to screen the most valuable radiomics features. Clinical-radiomics nomogram was developed by radiomics signatures and the most predictive clinical parameters. Prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis. RESULTS: For TD, the area under the receiver operating characteristic curve (AUC) for intratumoral radiomics model was 0.956, 0.823, and 0.860 in the training cohort, test cohort, and external validation cohort, respectively. AUC for the peritumoral radiomics model was 0.929, 0.906, and 0.773 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for combined intra- and peritumoral radiomics model was 0.976, 0.918, and 0.874 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for clinical-radiomics nomogram was 0.989, 0.777, and 0.870 in the training cohort, test cohort, and external validation cohort, respectively. The prognostic model constructed by combining intra- and peritumoral radiomics signature score (radscore)-based TD and MRI-reported lymph nodes metastasis (LNM) indicated good performance for predicting 3-year RFS, with AUC of 0.824, 0.865, and 0.738 in the training cohort, test cohort and external validation cohort, respectively. CONCLUSION: Combined intra- and peritumoral radiomics model showed good performance for predicting TD. Combining intra- and peritumoral radscore-based TD and MRI-reported LNM indicated the recurrence risk. CLINICAL RELEVANCE STATEMENT: Combined intra- and peritumoral radiomics model could help accurately predict tumor deposits. Combining this predictive model-based tumor deposits with MRI-reported lymph node metastasis was associated with relapse risk of rectal cancer after surgery. KEY POINTS: • Combined intra- and peritumoral radiomics model provided better diagnostic performance than that of intratumoral and peritumoral radiomics model alone for predicting TD in rectal cancer. • The predictive performance of the clinical-radiomics nomogram was not improved compared with the combined intra- and peritumoral radiomics model for predicting TD. • The prognostic model constructed by combining intra- and peritumoral radscore-based TD and MRI-reported LNM showed good performance for assessing 3-year RFS.

Lutein attenuates Propionibacterium acnes-induced inflammation by inhibiting pyroptosis of human keratinocyte cells via TLR4/NLRP3/Caspase-1 pathway.

BACKGROUND: Previous studies found Propionibacterium acnes (P. acnes) has a strong association with acne inflammation and cell pyroptosis. Because of the various side effects of current acne medicines, it is important to explore alternative drugs with anti-inflammatory activity against P. acnes. we explored the effect of Lutein on P. acnes-induced cell pyroptosis and accelerated the recovery of acne inflammation in vitro and vivo. METHODS: Lutein was utilized to expose HaCaT keratinocytes, then we reassessed the effect of Lutein on the cell apoptosis, pyroptotic-associated inflammatory factors and catabolic enzymes in heat-killed P. acnes-treated HaCaT cells. Next, living P. acnes was intradermally injected into the right ears of ICR mice to induce mice with acne inflammation, and the effect of Lutein on living P. acnes-induced inflammation was investigated. Moreover, we explored the mechanism of Lutein on TLR4/NLRP3/Caspase-1 pathways by ELISA, immunofluorescence microscopy, and western blot assay. RESULTS: Heat-killed P. acnes triggered remarkable cell pyroptosis, pyroptotic inflammatory factors and catabolic enzymes in HaCaT cells, including up-regulating interleukin (IL)-1ß, IL-18, TNF-α, MMP3, MMP13, ADAMTS4, and ADAMTS5, TLR4, NLRP3, caspase-1, and the ratio of gasdermin D to cleaved gasdermin D, whereas these effects were suppressed by Lutein. In addition, Lutein effectively improved ear redness, swelling, and the expression of TLR4, IL-1ß and TNF-α in vivo. Finally, NLRP3 activator (nigericin) increased caspase-1, IL-1ß and IL-18 level, while TLR4 inhibitor (TAK-242) significantly blocked this effect in heat-killed P. acnes-treated cells. CONCLUSIONS: Lutein attenuated P. acnes-caused pyroptosis of HaCaTs and the subsequent acne inflammation via the TLR4/NLRP3/Caspase-1 pathway.

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

Quality assessment of variable collagen tissues of sea cucumber (Stichopus japonicus) body wall under different heat treatment durations by label-Free proteomics analysis.

The microstructure of the body wall, body wall composition, and collagen fibers of sea cucumber (Stichopus japonicus) under different heating times (1 h, 4 h, 12 h, and 24 h) was investigated based on heat treatment at 80 °C. A Label-Free proteomics technique was applied to study the proteomic changes in the body wall of sea cucumbers under 4 and 12 h of heat treatment. Compared with the fresh group, 981 proteins were found to be differentially expressed proteins (DEPs) after heat treatment at 80 °C (4 h), and 1110 DEPs were observed after heat treatment at the same temperature for 12 h. There were 69 DEPs associated with mutable collagenous tissues (MCTs) structures. The results of correlation analysis showed that 55 DEPs were correlated with sensory properties, among which A0A2G8KRV2 was significantly correlated with hardness and SEM image texture features (SEM_Energy, SEM_Correlation, SEM_Homogeneity, and SEM_Contrast). These findings could be conducive to further comprehension of the structural changes and mechanisms of quality loss in the body wall of sea cucumbers at different heat treatment times.

Al-Incorporated Cobalt-Layered Double Hydroxides for Enhanced Oxygen Evolution through Morphology and Electronic Structure Regulation.

Layered double hydroxides (LDHs) are promising electrocatalytic materials for the oxygen evolution reaction (OER) due to their tunable composition and low cost. Here, we construct ultrathin Al-incorporated Co LDH nanosheets on carbon cloth (CC) by a facile hydrothermal strategy. Compared to Co LDH/CC, the optimized Co2Al1 LDH/CC displays significantly improved OER performance, characterized by low overpotentials of only 171 and 200 mV to reach current densities of 10 mA cm-2 in alkaline and neutral media, respectively, as well as good stability over an extended period. The introduced Al3+ and CC support play a synergistic role in steering the morphology of Co2Al1 LDH/CC while also increasing the electrochemical active sites. X-ray absorption fine spectra (XAFS) analyses uncover the critical role of Al in regulating the coordination environment of Co atoms, with evidence affording highly active Co oxidation states. Moreover, density functional theory (DFT) calculations confirmed that the Al3+ incorporated into Co LDH/CC can efficaciously modulate the electronic density of states of the d-band center of Co atoms, optimize the Gibbs free energies of intermediates toward OER, and thus accelerate the O2 evolution rate.