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To investigate the differences in serum tryptophan, lysine, and phenylalanine levels in breast cancer patients, the correlation between the three amino acids with the chemotherapy regimen, and their significance in the clinical diagnosis and treatment of breast cancer. Clinical data were collected from the Department of Breast Surgery at Yunnan Cancer Hospital, encompassing 216 cases from July to December 2020, including 91 healthy individuals, 38 with benign tumors, and 87 with cancer. Amino acid levels were measured using liquid chromatography-tandem mass spectrometry. Statistical analyses, such as the Kruskal-Wallis H-test and Wilcoxon test, were conducted to compare the levels of these amino acids across the healthy group, benign tumor group, and breast cancer group. The χ2 test and Fisher's exact probability method were employed to assess the relationship between amino acid levels and breast cancer stage, grade, and chemotherapy regimen. The results indicated that there were significant differences in serum lysine (H = 36.13, P .05) and phenylalanine (F = 1.466, P > .05) levels across different conventional chemotherapy regimens among the breast cancer cases studied. Serum lysine and phenylalanine levels might serve as potential biomarkers for breast cancer, and the choice of chemotherapy regimen is unlikely to impact significant changes in these amino acid levels.

Background: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. Objective: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. Materials and methods: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein–protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. Results: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. Conclusion: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.

Schwannoma (syn. neurilemoma, neuroschwannoma) is a benign tumor derived from nerve sheath cells (Schwann cells), which is the most common type of peripheral neurogenic tumors. In this case, a patient with papillary thyroid carcinoma on the left side was found to have a predominantly cystic nodule in the ipsilateral neck level 4 by ultrasonography (US), which mistook for ipsilateral cervical lymph node metastasis and was later found to be a vagal nerve sheath tumor by surgery. The article reviews the pathology, imaging findings and differential diagnosis of schwannomas. A meticulous evaluation and comprehensive differential diagnosis are pivotal to reach correct diagnosis.

Colorectal cancer (CRC) is associated with numerous genetic disorders and cellular abnormalities, and liver metastasis is a common health concern in patients with CRC. Exploring newer and more efficient therapies to block liver metastasis is pivotal for prolonging patient survival. Therefore, small interfering RNAs (siRNAs) are expected to be remarkable tools capable of regulating gene expression by participating in a process called RNA interference (RNAi). RNAi is a biological process among eukaryotes wherein specific messenger RNA (mRNA) molecules are destroyed and gene expression is inhibited. This technology is a promising therapeutic agent in the treatment of CRC liver metastasis (CRLM). Nevertheless, crucial problems in siRNA therapeutics, including inherent poor serum stability and nonspecific uptake into biological systems, must be recognized. For this reason, delivery systems are being developed in an attempt to solve these problems. Here, we discuss the utility of siRNA therapy for the treatment of CRCLM by targeting the major metastasis-related signaling pathways. siRNA therapy has the potential to be one of the most effective methods for CRLM treatment in the future.

Cancer patients experience an increased risk of venous thromboembolism (VTE). In this study, we investigated a risk of venous thromboembolism algorithm (RVTA) in patients with colorectal cancer and evaluated its ability to predict the prognosis of colorectal cancer. We retrospectively analyzed clinical data from 345 patients with colorectal cancer from January 2015 to December 2018 at the Shanghai Cancer Center to develop the RVTA. Additionally, the 345 patients were followed until December 2020 for prognostic analysis. The RVTA included the following variables: (a) platelet count, (b) blood transfusion history, (c) metastasis, (d) multiple chemotherapy regimens, and (e) the D-dimer level. Good predictive efficiency was observed for the RVTA (AUC was 0.825; 95% CI was 0.721 to 0.930). The median progression-free survival (PFS) of patients who had a score less than 4 (0-3), defined as the low-risk group, was significantly longer than that of the high-risk group, which included patients who had a score greater than 4 (4-8) (26 vs ten months, P

The annual incidence of papillary thyroid carcinoma has increased dramatically. T cell factor 4 (TCF4) is an important component of Wnt signaling pathway.However, the role of TCF4 in PTC remains unknown. In this study, TCF4 was observed to overexpress in PTC patients and cells by qRT-PCR assay. The colony formation assay, Edu staining and transwell assay indicated thatoverexpression of TCF4 promoted cell proliferation and invasion of TCP-1 cells, whereas knockdown of TCF4 inhibited cell proliferation and invasion of IHH-4 cells. To investigate the mechanism of TCF4 in PTC cells, the luciferase assay demonstrated that TCF4 could modulate HCP5 expression. Besides, GLuc-ON promoter reporter assayproved that TCF4 could bind to HCP5 promoter. Further, knockdown of HCP5 could significantly up-regulated miR-15a, miR-216a-5p, miR-22-3p, miR-139-5p, miR-203, miR-27a-3p and miR-320, and down-regulated miR-186-5p in IHH-4 cells, which might be potential downstream of TFC4/HCP5 axis. In conclusion, up-regulation TCF4 can promote HCP5 expression via binding to HCP5 promoter. It may be the first time to prove that TCF4 regulates HCP5 in PTC, which provides a novel sight for treatment of PTC.

Purpose: Discoidin domain receptor 1 (DDR1) belongs to a novel class of receptor tyrosine kinases. Previous evidence indicates that DDR1 overexpression promotes the aggressive growth of bladder cancer (BC) cells. This study aimed to investigate the molecular mechanisms by which DDR1 influences BC. Methods: DDR1 was transfected into human BC RT4 cells. DDR1, COL4A1, and MMP-2 expression in 30 BC tissues and paired adjacent tissues were examined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Transwell assays were conducted to determine cell migration and invasion. RT-PCR and western blot (WB) were also used to measure the DDR1, COL4A1, MMP-2, and EMT-related gene (ZEB1 and SLUG) expression in RT4 cells after DDR1 overexpression. Results: COL4A1 and MMP-2 interacted with DDR1 in the PPI network. RT-PCR and immunohistochemistry results showed that both mRNA and protein levels of DDR1 and COL4A1 were significantly increased in BC tissue, while the expression of MMP-2 was increased only at the mRNA level ( P < 0.05). Overexpression of DDR1 in RT4 cells significantly promoted their migratory and invasive capabilities in vitro ( P < 0.05). Moreover, overexpression of DDR1 in RT4 cells increased the mRNA and protein expression of ZEB1, SLUG, COL4A1, and MMP-2 ( P < 0.01). DDR1-mediated migration and invasion of RT4 cells were reversed after COL4A1-siRNA treatment. Conclusion: DDR1 may be a potential therapeutic target in BC patients.

Background: Osteoarthritis is a degenerative disease that commonly occurs in middle-aged and elderly people. High-quality articles in the field of osteoarthritis rehabilitation have not been studied in detail. Objective: To identify and conduct a qualitative and quantitative analysis of the 50 most-cited articles on osteoarthritis rehabilitation and provide valuable scientific information for researchers. Methods: Fifty articles related to the rehabilitation of individuals with osteoarthritis were retrieved from the Web of Science Core Collection. Basic information, such as the authors, title, number of citations, year of publication, journal, country/territory, and research type, was extracted. CiteSpace was used to visualize the keywords. Results: The average number of citations per article was 244.54. The top 50 articles were published in 27 journals and published by 262 authors. Most of the top 50 articles were published in the United States. The top 50 articles included 23 randomized controlled trials, 21 cohort studies, 2 case series, and 4 expert opinion articles. The most commonly studied topics in osteoarthritis rehabilitation included rehabilitation for pain, gait abnormalities, muscle strength deficiencies, and other functional impairments caused by osteoarthritis in elderly people. Conclusions: The top articles in the field of osteoarthritis rehabilitation have a high level of evidence. Collaboration between authors was high for highly-cited articles. Moreover, the eminent articles can provide important information for the education of doctors and therapists specializing in osteoarthritis rehabilitation.

Objective: The present study aimed to detect A-kinase interacting protein 1 expression and further explore the association of A-kinase interacting protein 1 with clinical features and prognosis in patients with multiple myeloma. Methods: Totally, 152 de novo symptomatic patients with multiple myeloma and 30 healthy donors were enrolled. Bone marrow mononuclear cells derived plasma cells were collected from patients with multiple myeloma before initial treatment and from healthy donors on the enrollment, respectively, and then A-kinase interacting protein 1 protein/messenger RNA expressions were detected by Western blot and reverse transcription quantitative polymerase chain reaction. Treatment response (complete response and overall response rate) was assessed, and survival profiles (progression-free survival and overall survival) were calculated in patients with multiple myeloma. Results: A-kinase interacting protein 1 protein/messenger RNA expressions were elevated in patients with multiple myeloma compared to healthy donors, and A-kinase interacting protein 1 (area under the curve: 0.809, 95% confidence interval: 0.726-0.891)/messenger RNA (area under the curve: 0.839, 95% confidence interval: 0.764-0.914) presented good value in differentiating patients with multiple myeloma from healthy donors. In patients with multiple myeloma, A-kinase interacting protein 1 /messenger RNA expressions negatively correlated with albumin while positively correlated with Beta-2-microglobulin, lactate dehydrogenase, International Staging System stage, and t (4;14). Meanwhile, there were 39 (25.7%) complete response patients, 113 (74.3%) noncomplete response patients, 112 (73.7%) overall response rate patients, and 40 (26.3%) nonoverall response rate patients. Complete response and overall response rates were decreased in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. Additionally, progression-free survival and overall survival were reduced in patients with high A-kinase interacting protein 1 compared to patients with low A-kinase interacting protein 1. Conclusion: A-kinase interacting protein 1 exhibits the potency as a biomarker for multiple myeloma progression and prognosis, which implies the clinical application of A-kinase interacting protein 1 in multiple myeloma management.

Objective: This study aimed to investigate the correlation of long noncoding RNA plasmacytoma variant translocation 1 with clinical features and prognosis in patients with multiple myeloma. Methods: The bone marrow samples were collected from 128 patients with de novo symptomatic multiple myeloma (before initial treatment) and 30 healthy donors (on the enrollment). Long noncoding RNA plasmacytoma variant translocation 1 expression in bone marrow-derived plasma cells was detected by reverse transcription quantitative polymerase chain reaction. In patients with multiple myeloma, their demographics and clinical features before treatment were collected; induction treatment response (complete response and overall response rate) and survival profiles (progression-free survival and overall survival) were assessed. Results: Expression of long noncoding RNA plasmacytoma variant translocation 1 was increased in patients with multiple myeloma compared to healthy donors. Receiver-operating characteristic curve showed that long noncoding RNA plasmacytoma variant translocation 1 distinguished patients with multiple myeloma from healthy donors with an area under the curve of 0.884 (95% confidence interval: 0.829-0.940). In patients with multiple myeloma, high expression of long noncoding RNA plasmacytoma variant translocation 1 correlated with elevated β-2 microglobulin, increased International Staging System stage, and raised Del (17p), but it did not correlate with other biochemical indexes or chromosomal abnormalities. Furthermore, long noncoding RNA plasmacytoma variant translocation 1 high expression patients presented with decreased complete response and overall response rate compared to long noncoding RNA plasmacytoma variant translocation 1 low expression patients, and high expression of long noncoding RNA plasmacytoma variant translocation 1 predicted unfavorable progression-free survival as well overall survival in patients with multiple myeloma. Conclusion: Long noncoding RNA plasmacytoma variant translocation 1 might be a potential biomarker for the supervision of disease progression and prognosis in patients with multiple myeloma.

Secondary hemorrhage occurs as a complication of central nervous system (CNS) following acupuncture has been reported in few cases. The present study reports a case of a 70-year-old woman who presents medulla oblongata hemorrhage after acupuncture. The patient suffered severe headache, neck pain, vomiting, and weakness after the neck acupuncture. The purpose of presenting this case report is to raise awareness among clinicians of fateful CNS complications during acupuncture. More importantly, qualified training of acupuncturists is anticipated and standardized processes of clinical acupuncture operations needs to be developed, in order to avoid the occurrence of acupuncture accidents. Keywords: Secondary hemorrhage, Medulla oblongata, Acupuncture, Complication

Many studies have investigated the efficacy of Endostar combined with transcatheter arterial chemoembolization (TACE) versus TACE alone for hepatocellular carcinoma (HCC). A systematic review was conducted to evaluate the efficacy of Endostar. PubMed, Embase, and other databases were searched, and meta-analysis was performed using RevMan 5.3 software. Nine studies, all of which were clinical randomized controlled trials, involving 411 participants were included. The overall response rate, disease control rate and α-fetoprotein negative conversion ratio, and the 6- and 12-month survival rate of HCC patients treated with combined Endostar and TACE were higher than those treated with TACE alone ( P < .01). Furthermore, the incidence of tumor progression was low after Endostar treatment ( P = .005). The incidence of adverse effects (leukocytopenia, liver function damage, and vomiting) was similar in Endostar with TACE and in TACE alone ( P > .05). However, large studies and more randomized trials are necessary to determine the effects of Endostar on HCC.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development. In this study, we isolated 44 natural products from deep-sea-derived fungi and identified isobisvertinol ( 17 ) as a compound with anti-inflammatory and ferroptosis-inhibiting effects. Using LPS-induced microglial inflammation and RSL3-induced neuronal ferroptosis models, we found that 17 targets TLR4 to provide neuroprotection. Molecular docking studies revealed that 17 inhibits TLR4 activation by occupying the hydrophobic pocket at the TLR4-MD2 binding site. Additionally, 17 suppresses TLR4, reducing p38 MAPK phosphorylation, and inhibits ferroptosis by decreasing lipid peroxidation and modulating mitochondrial membrane potential. Metabolomic analysis showed that 17 rescues alterations in multiple metabolic pathways induced by RSL3 and increases levels of antioxidant metabolites, including glutamine, glutamate, and glutathione. In summary, our results indicate that isobisvertinol ( 17 ) targets TLR4 in neural cells to reduce inflammation and inhibit p38 MAPK phosphorylation, while regulating metabolic pathways, mainly GSH synthesis, to provide antioxidant effects and prevent ferroptosis in neurons.

Objectives: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing condition linked to the accelerated onset of mild cognitive impairment (MCI). However, the prevalence of undiagnosed MCI among OSA patients is high and attributable to the complexity and specialized nature of MCI diagnosis. Timely identification and intervention for MCI can potentially prevent or delay the onset of dementia. This study aimed to develop screening models for MCI in OSA patients that will be suitable for healthcare professionals in diverse settings and can be effectively utilized without specialized neurological training., Methods: A prospective observational study was conducted at a specialized sleep medicine center from April 2021 to September 2022. Three hundred and fifty consecutive patients (age: 18-60 years) suspected OSA, underwent the Montreal Cognitive Assessment (MoCA) and polysomnography overnight. Demographic and clinical data, including polysomnographic sleep parameters and additional cognitive function assessments were collected from OSA patients. The data were divided into training (70%) and validation (30%) sets, and predictors of MCI were identified using univariate and multivariate logistic regression analyses. Models were evaluated for predictive accuracy and calibration, with nomograms for application., Results: Two hundred and thirty-three patients with newly diagnosed OSA were enrolled. The proportion of patients with MCI was 38.2%. Three diagnostic models, each with an accompanying nomogram, were developed. Model 1 utilized body mass index (BMI) and years of education as predictors. Model 2 incorporated N1 and the score of backward task of the digital span test (DST&#95;B) into the base of Model 1. Model 3 expanded upon Model 1 by including the total score of digital span test (DST). Each of these models exhibited robust discriminatory power and calibration. The C-statistics for Model 1, 2, and 3 were 0.803 [95% confidence interval (CI): 0.735-0.872], 0.849 (95% CI: 0.788-0.910), and 0.83 (95% CI: 0.763-0.896), respectively., Conclusion: Three straightforward diagnostic models, each requiring only two to four easily accessible parameters, were developed that demonstrated high efficacy. These models offer a convenient diagnostic tool for healthcare professionals in diverse healthcare settings, facilitating timely and necessary further evaluation and intervention for OSA patients at an increased risk of MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Fan, Xie, Yang and Zeng.)

Background : Previous studies on the association between diet quality and ovarian cancer (OC) survival are limited and inconsistent. We evaluated the relationship between pre- and post-diagnosis diet quality based on the Healthy Eating Index-2020 (HEI-2020), as well as their changes and OC survival. Methods : This prospective cohort study involved 1082 patients with OC aged 18-79 years, enrolled between 2015 and 2022. Detailed dietary intake before and after diagnosis was recorded using a validated food frequency questionnaire. Deaths were ascertained until February 16th, 2023 via medical records and active follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results : We included 549 OC cases with a median follow-up of 44.9 months, representing 206 total deaths. Higher HEI scores were associated with better OS (pre-diagnosis: HR T3 vs. T1 0.66, 95%CI: 0.46-0.93, HR 1-SD 0.84, 95%CI: 0.73-0.96; post-diagnosis: HR T3 vs. T1 0.68, 95%CI: 0.49-0.96, HR 1-SD 0.80, 95%CI: 0.69-0.92). Compared to the stable group, the group with decreased HEI scores (>3%) from pre- to post-diagnosis had worse OS (HR 1.93, 95%CI: 1.26-2.97). Conclusion : High pre- and post-diagnosis diet quality was associated with improved OC survival, whereas deterioration in diet quality after diagnosis was associated with decreased OC survival.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 μM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg -1 ·d -1 , i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. Cortical slow oscillations drive the repeated reactivation of hippocampal memory representations together with SWRs and thalamo-cortical spindles, inducing long-lasting cellular and network modifications responsible for memory stabilization.In this review, we aim to comprehensively cover the field of "reactivation and memory consolidation" research by detailing the physiological mechanisms of neuronal reactivation and firing patterns during SWRs and providing a discussion of more recent key findings. Several mechanistic explanations of neuropsychiatric diseases propose that impaired neural replay may underlie some of the symptoms of the disorders. Abnormalities in neuronal reactivation are a common phenomenon and cause pathological impairment in several diseases, such as Alzheimer's disease (AD), epilepsy and schizophrenia. However, the specific pathological changes and mechanisms of reactivation in each disease are different. Recent work has also enlightened some of the underlying pathological mechanisms of neuronal reactivation in these diseases. In this review, we further describe how SWRs, ripples and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

The ankle joint, which connects the lower limbs and the sole of the foot, is prone to sprain during walking and sports, which leads to ankle arthritis. Supratroleolar osteotomy is an ankle preserving operation for the treatment of ankle arthritis, in which the osteotomy is an important fixing and supporting part. In order to avoid stress shielding effect as much as possible, the osteotomy block is designed as a porous structure. In this study, the osteotomy block was designed based on three-period minimal surface, and the designed structure was manufactured by 3D printing. The mechanical properties of different structures were studied by mechanical test and finite element simulation. In mechanical tests, the Gyroid structure showed a progressive failure mechanism from bottom to bottom, while the Diamond structure showed a shear failure zone at 45° Angle, which was not conducive to energy absorption and was more prone to brittle fracture than the Gyroid structure. Therefore, the Gyroid structure is valuable for further research in the development of porous osteotomy., (© 2024. The Author(s).)

Three new C 10 and C 12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC 50 value of 120.3 nM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In this study, a Ti 3 C 2 MXene@g-C 3 N 4 composite powder (TM-CN) was prepared by the ultrasonic self-assembly method and then loaded onto a carbon nanofiber membrane by the self-assembly properties of MXene for the treatment of organic pollutants in wastewater. The characterization of the TM-CN and the C-TM-CN was conducted via X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometer (FTIR) to ascertain the successful modification. The organic dye degradation experiments demonstrated that introducing an appropriate amount of Ti 3 C 2 MXene resulted in the complete degradation of RhB within 60 min, three times the photocatalytic efficiency of a pure g-C 3 N 4 . The C-TM-CN exhibited the stable and outstanding photocatalytic degradation of the RhB solution over a wide range of pH values, indicating the characteristics of the photodegradation of organic pollutants in a wide range of aqueous environments. Furthermore, the results of the cyclic degradation experiments demonstrated that the C-TM-CN composite film maintained a degradation efficiency of over 85% after five cycles, thereby confirming a notable improvement in its cyclic stability. Consequently, the C-TM-CN composite film exhibits excellent photocatalytic performance and is readily recyclable, making it an auspicious eco-friendly material in water environment remediation.

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC 50 value of 3.0 μM, 0.4 μM, and 0.1 μM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities., 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. Published by Elsevier Inc.)

Objective: To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum., Methods: A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template. In 3D-printing group, there were 14 patients, including 10 males and 4 females； aged from 21 to 53 years old；CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted. In conventional group, there were 15 patients, including 10 males and 5 females；aged from 19 to 55 years old；conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted. Blood loss, surgical time, radiographic quality of reduction, and hip function were compared between groups., Results: The difference in operation time and intraoperative blood loss was significant（ P <0.05）. Twenty-three patients were followed up from 12 to 30 months, and the fractures in both groups healed with a healing time of 3 to 6 months. At the last follow-up, the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conventional group（ P <0.05）, with no significant differences in walking ability, hip mobility and total score（ P >0.05）. In 3D printing group, 6 cases were excellent, 5 cases were good, 3 cases were fair；in conventional group, 5 cases were excellent, 5 cases were good, 4 cases were fair, 1 case was worse；no significant difference between two groups（ P >0.05）., Conclusion: Virtual preoperative planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery, improve the quality of reduction. This method is efficient, accurate and reliable to treat acetabular posterior wall fractures.

Background: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking., Objective: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo., Methods: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing., Results: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125., Conclusion: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway., Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023. Published by Elsevier GmbH.)

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C ( 1 - 3 ) and one novel hybrid polyketide hepialide ( 4 ), together with 18 known miscellaneous compounds ( 5 - 22 ). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8 , 11 , 13 , 21 , and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC 50 value of 426.2 nM.

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC 50 =2.0 μM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 μM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Three new polyketides (penidihydrocitrinins A-C, 1 - 3 ) and fourteen known compounds ( 4 - 17 ) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1 - 17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC 50 value of 4.7 µM. Additionally, compounds 6 , 7 , and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 μM, 5.0 μM, and 10 μM.

Marine fungi are prolific source for the discovery of structurally diverse and bioactive molecules. In our search for new anti-osteoporosis compounds from deep-sea-derived fungi, we prioritized a fungus whose extract exhibited moderate activity and rich chemical diversity. The investigation of this strain afforded a class of citrinins, including three new citrinin trimers, neotricitrinols A-C (1-3), and three known dimeric/monomeric precursors (4-6). Neotricitrinols A-C (1-3) feature a unique octacyclic carbon scaffold among the few reported citrinin trimers with their absolute configurations established by spectroscopic analysis, theoretical-statistical approaches (GIAO-NMR, TDDFT-ECD/ORD calculations), DP4+ probability analysis as well as biogenetic consideration. A plausible biosynthetic pathway linking 1-3 from the common intermediate metabolite penicitrinol A (4) was proposed. Biologically, neotricitrinol B (2) showed potential anti-osteoporosis activity by promoting osteoblastogenesis and inhibiting adipogenic differentiation on primary bone mesenchymal stem cells, while displaying no cytotoxicity., 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 © 2023 Elsevier Inc. All rights reserved.)

A systematic chemical investigation of the deep-sea-derived fungus Aspergillus versicolor 170217 resulted in the isolation of six new ( 1 - 6 ) and 45 known ( 7 - 51 ) compounds. The structures of the new compounds were established on the basis of exhaustive analysis of their spectroscopic data and theoretical-statistical approaches including GIAO-NMR, TDDFT-ECD/ORD calculations, DP4+ probability analysis, and biogenetic consideration. Citriquinolinones A ( 1 ) and B ( 2 ) feature a unique isoquinolinone-embedded citrinin scaffold, representing the first exemplars of a citrinin-isoquinolinone hybrid. Dicitrinones K-L ( 3 - 4 ) are two new dimeric citrinin analogues with a rare CH-CH 3 bridge. Biologically, frangula-emodin ( 32 ) and diorcinol ( 17 ) displayed remarkable anti-food allergic activity with IC 50 values of 7.9 ± 3.0 μM and 13.4 ± 1.2 μM, respectively, while diorcinol ( 17 ) and penicitrinol A ( 20 ) exhibited weak inhibitory activity against Vibrio parahemolyticus , with MIC values ranging from 128 to 256 μM.

Background: Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion., Cases: We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications., Conclusion: Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2023 by the Wound, Ostomy and Continence Nurses Society.)

Objectives: To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture., Methods: Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA 0 group (received one session of EA), EA 6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA 48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han 's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA 6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*)., Results: The amplitude of MEPs at T1 and T2 in the EA 0 group, at T0* in the EA 6h group and at T1, T2 and T3 in the EA 48h group was higher when compared with the value at T0 in each group separately ( P <0.001). At T1, the amplitude of MEPs in the EA 0 group and the EA 48h group was higher than that in the EA 6h group ( P <0.001, P <0.01); at T2, it was higher in the EA 0 group when compared with that in the EA 6h group ( P <0.01); at T3, the amplitude in the EA 0 group and the EA 6h group was lower than that of the EA 48h group ( P <0.001). The LAT at T1 was shorter than that at T0 in the three groups ( P <0.05), and the changes were not obvious at the rest time points compared with that at T0 ( P > 0.05). The GPT completion time of healthy subjects in the EA 0 group and the EA 48h group at T1, T2 and T3 was reduced in comparison with that at T0 ( P <0.001). The completion time at T3 was shorter than that at T0 in the EA 6h group ( P <0.05); at T2, it was reduced in the EA 48h group when compared with that of the EA 6h group ( P <0.05). There were no significant differences in rMT among the three groups and within each group ( P >0.05)., Conclusions: Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work. This work described has not been published previously (except in the form of an abstract, a published lecture or academic thesis, see 'Multiple, redundant or concurrent publication' for more information), that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Signal regulatory protein (SIRPα) is an immune inhibitory receptor expressed by myeloid cells to inhibit immune cell phagocytosis, migration, and activation. Despite the progress of SIRPα and CD47 antagonist antibodies to promote anti-cancer immunity, it is not yet known whether SIRPα receptor agonism could restrain excessive autoimmune tissue inflammation. Here, we report that neutrophil- and monocyte-associated genes including SIRPA are increased in inflamed tissue biopsies from patients with rheumatoid arthritis and inflammatory bowel diseases, and elevated SIRPA is associated with treatment-refractory ulcerative colitis. We next identify an agonistic anti-SIRPα antibody that exhibits potent anti-inflammatory effects in reducing neutrophil and monocyte chemotaxis and tissue infiltration. In preclinical models of arthritis and colitis, anti-SIRPα agonistic antibody ameliorates autoimmune joint inflammation and inflammatory colitis by reducing neutrophils and monocytes in tissues. Our work provides a proof of concept for SIRPα receptor agonism for suppressing excessive innate immune activation and chronic inflammatory disease treatment., Competing Interests: Declaration of interests All authors except D.A.F. are current or past employees of Genentech, a member of the Roche group, and may hold Roche stock or stock options., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A (1) and 25 known secondary metabolites (2-26). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC 50 values of 1.4 μM and 6.7 μM, respectively., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Two new xanthones ( 1 and 2 ) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds ( 3 - 36 ). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC 50 values of 5.5 and 3.5 μM, respectively, whereas 26 , 28 , 33 , and 34 significantly inhibited RSL3-induced ferroptosis, with EC 50 values of 11.6, 7.2, 11.8, and 2.2 μM, respectively.

Objective: To compare the efficacy and safety of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) and neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced middle and low rectal cancer. Methods: A retrospective cohort study was carried out. A of 126 patients with locally advanced middle and low rectal cancer who were treated in the Department of Gastrointestinal Cancer Surgery of Fujian Cancer Hospital from September 2016 to March 2020 were enrolled, including 73 males and 53 females, with a mean age of (56.5±9.8) (23-77) years. Based on neoadjuvant regimen (nCRT treatment was performed before December 2018 and SCRT-TNT treatment was carried out after January 2019), patients were divided into nCRT group ( n =68) and SCRT-TNT group ( n =58). There were no statistically significant differences in age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage between the two groups (all P>0.05). Patients in both groups received pelvic intensity-modulated radiotherapy (IMRT). The radiotherapy dose of nCRT group was 50Gy/25 times/5 weeks. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. However, patients in SCRT-TNT group received CapeOX regimen (oxaliplatin+capecitabine) for 2 cycles of induction chemotherapy, followed by short-course radiotherapy (25Gy/5 times/5 days), then underwent a radical surgery two weeks after completion of consolidation chemotherapy (4 cycles). The adverse reactions, perioperative safety and efficacy of neoadjuvant therapy were compared and analyzed between the two groups. Results: Both groups completed neoadjuvant therapy as planned. Patients in nCRT group and SCRT-TNT group had similar incidence of adverse reactions to radiotherapy and chemotherapy, however, there were no statistically significant differences in the incidence of surgical complications, operation time, intraoperative blood loss and postoperative length of hospital stay (all P >0.05). A total of 119 patients underwent total mesenterectomy (TME), including 64 patients in the nCRT group and 55 patients in the SCRT-TNT group, all with R0 resection. The pathological complete response (pCR) rate was 10.9% (7/64) in the nCRT group and 25.5% (14/55) in the SCRT-TNT group, respectively, with a statistically significant difference ( P =0.038). Two years after surgery, there was no statistically significant difference in local recurrence rate and overall survival rate between the two groups (both P >0.05). However, the clinical metastasis rate of SCRT-TNT group was significantly lower than that of nCRT group (20.3% vs 9.1%), with a statistically significant difference ( P <0. 05). Conclusion: SCRT-TNT do not increase the adverse reactions of radio chemotherapy and perioperative risks in the treatment of locally advanced middle and low rectal cancer, and the tumor regression effect is good, which is worthy of clinical promotion.

Chemical investigation of the deep-sea-derived fungus Rhizopus sp. W23 resulted in the identification of six new ( 1 - 3 , 6 , 8 , 9 ) and 12 known ( 4 , 5 , 10 - 19 ) cyclocitrinol analogues, together with one handling artifact ( 7 ), all featuring an unusual 7/7/6/5-tetracyclic scaffold and bicyclo[4.4.1] A/B rings. Norcyclocitrinoic acids A and B ( 1 , 2 ) represent the second occurrence of 24,25-bisnor cyclocitrinols. Structures were assigned to new steroids on the basis of extensive spectroscopic analysis and X-ray crystallography. Compound 13 significantly enhances osteoblastogenesis and inhibits adipogenesis in mature bone marrow stromal cells at 5 μM, indicating a potential to be an antiosteoporosis lead.

Choroidal neovascularization (CNV) is a hallmark of wet age-related macular degeneration, which severely impairs central vision. Studies have shown that endothelial-mesenchymal transition (EndMT) is involved in the pathogenesis of CNV. Licochalcone A (lico A), a flavonoid extracted from the root of licorice, shows the inhibition on EndMT, but it remains unclear whether it can suppress the formation of CNV. The aim of this study is to investigate the effects of lico A on laser-induced CNV, and EndMT process in vitro and vivo. We established the model of CNV with a krypton laser in Brown-Norway rats and then intraperitoneally injected lico A. Our experimental results demonstrated that the leakage of CNV was relieved, and the area of CNV was reduced in lico A-treated rats. Cell migration and tube formation in oxidized low-density lipoprotein (Ox-LDL)-stimulated HUVECs were inhibited by lico A and promoted by PI3K activator 740Y-P. The protein expressions of snai1 and α-SMA were increased, and CD31 and VE-cadherin were decreased in the model rats of CNV, but partially reversed after treatment with lico A. The expression of CD31 was decreased and α-SMA was increased in OX-LDL-treated HUVECs, which was further strengthened by 740Y-P, while the expression of CD31 was up-regulated and α-SMA was down-regulated in lico A treated HUVECs. Our data revealed that EndMT process was alleviated by lico A. Meanwhile, PI3K/AKT signaling pathway was activated in model rat of CNV and Ox-LDL-stimulated HUVECs, which can be suppressed with treatment of lico A. Our experimental results confirmed for the first time that lico A has the potential to alleviate CNV by inhibiting the endothelial-mesenchymal transition via PI3K/AKT signaling pathway., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The Cladosporium fungi, one of the largest genera of dematiaceous hyphomycetes, could produce various bioactive secondary metabolites. From the AcOEt-soluble extract of Cladosporium oxysporum 170103, three new secopatulolides (1-3) and thirteen known compounds (4-16) were obtained. Their structures were established by detailed analysis of the NMR and HR-ESI-MS data. All sixteen compounds were tested for antibacterial activity against Vibrio parahemolyticus, ergosterol (10) presented moderate effect with the minimum inhibitory concentration (MIC) of 32 μM. It can destruct the membrane integrity of Vibrio parahemolyticus to change the cell shape., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Tumor metastasis is a common event in patients with gastric cancer (GC) who previously underwent curative gastrectomy. It is meaningful to employ high-volume clinical data for predicting the survival of metastatic GC patients. We aim to establish an improved machine learning (ML) classifier for predicting if a patient with metastatic GC would die within 12 months. Eligible patients were enrolled from a Chinese GC cohort, and the complete detailed information from medical records was extracted to generate a high-dimensional dataset. Appropriate feature engineering and feature filter were conducted before modeling with eight algorithms. A 10-fold cross validation (CV) nested in a holdout CV (8:2) was employed for hyperparameter tuning and model evaluation. Model selection was based on the area under the receiver operating characteristic (AUROC) curve, recall, and precision. The selected model was globally explained using interpretable surrogate models. Of the total 399 cases (median survival of 8.2 months), 242 patients survived less than 12 months. The linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) model had the highest AUROC (0.78 ± 0.021), recall (0.93 ± 0.031), and precision (0.80 ± 0.026), respectively. The LDA model created a new function that generally separated the two classes. The predicted probability of the SVM model was interpreted using a linear regression model visualized by a nomogram. The predicted class of the RF model was explained using a decision tree model. In summary, analyzing high-volume medical data by ML is helpful to produce an improved model for predicting the survival in patients with metastatic GC. The algorithm should be carefully selected in different practical scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhang, Yang, Xu, Zhang, Wu, Xie, Feng, Feng and Ma.)

Six new citreoviridins (citreoviridins J-O, 1 - 6 ) and twenty-two known compounds ( 7 - 28 ) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O ( 1 - 6 ) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A ( 7 ), terrein ( 14 ), and citreoviridin ( 20 ) significantly induced apoptosis for HeLa cells with IC 50 values of 5.4 μ M, 11.3 μ M, and 0.7 μ M, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.

Background: Clinical studies of type 2 (T2) cytokine-related neutralizing antibodies in asthma have identified a substantial subset of patients with low levels of T2 inflammation who do not benefit from T2 cytokine neutralizing antibody treatment. Non-T2 mechanisms are poorly understood in asthma but represent a redefined unmet medical need., Objective: We sought to gain a better understanding of genetic contributions to T2-low asthma., Methods: We utilized an unbiased genome-wide association study of patients with moderate to severe asthma stratified by T2 serum biomarker periostin. We also performed additional expression and biological analysis for the top genetic hits., Results: We identified a novel protective single nucleotide polymorphism at chr19q13.41, which is selectively associated with T2-low asthma and establishes Kallikrein-related peptidase 5 (KLK5) as the causal gene mediating this association. Heterozygous carriers of the single nucleotide polymorphisms have reduced KLK5 expression. KLK5 is secreted by human bronchial epithelial cells and elevated in asthma bronchial alveolar lavage. T2 cytokines IL-4 and IL-13 downregulate KLK5 in human bronchial epithelial cells. KLK5, dependent on its catalytic function, induces epithelial chemokine/cytokine expression. Finally, overexpression of KLK5 in airway or lack of an endogenous KLK5 inhibitor, SPINK5, leads to spontaneous airway neutrophilic inflammation., Conclusion: Our data identify KLK5 to be the causal gene at a novel locus at chr19q13.41 associated with T2-low asthma., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

From the deep-sea-derived Fusarium sp. ZEN-48, four known compounds were obtained. Their structures were established by extensive analyses of the NMR, HR-ESI-MS, and the X-ray crystallographic data as brefeldin A (BFA, 1), brevianamide F (2), N-acetyltryptamine (3), and (+)-diaporthin (4). Although BFA was extensively investigated for its potent bioactivities, its role on TNFα-induced necroptosis was incompletely understood. In this study, BFA showed significant inhibition on TNFα-induced necroptosis by disrupting the necrosome formation and suppressing the phosphorylation of RIPK3 and MLKL (IC 50 =0.5 μM). While, it had no effect on TNFα-induced NF-κB/MAPKs activation and apoptosis. The finding raised significant implications of BFA for necroptosis-related inflammatory disease therapy and new drug development from marine fungi., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Antibodies produced by plasma cells are a major arm of adaptive immunity. Germinal center reactions that include germinal center B cells and follicular T cells are fundamental players for antibody production, particularly antigen specific antibodies. Here we describe multiple methods that we and others have developed to analyze the production of antigen-specific antibodies in mice, with protocols for assessing antibody affinity and antibody isotype. The detection of antigen-specific IgE in serum using a traditional enzyme-linked immunosorbent assay (ELISA) method is often problematic due to much higher amounts of IgG. Thus we provide a specialized protocol for the detection of antigen-specific IgE in serum using ELISA., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide ( 1 ), two new alkaloids ( 2 and 3 ), and 22 known ( 4 - 2 5 ) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol ( 13 ) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC 50 values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC 50 value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester ( 9 ) and penicopeptide A ( 10 ) showed moderate effects (IC 50 = 50 and 58 μM, respectively).

Background: Reconstructing bone structures and stabilizing adjacent joints are clinical challenges in treating talar necrosis and collapse (TNC). 3D printing technology has been demonstrated to improve the accuracy of talar replacement. This study aimed to evaluate anatomical talar replacement and the clinical results., Methods: Nine patients with TNC were enrolled between 2016 and 2020. The prosthetic shape and size were designed by CT post-processing and mirror symmetry technology. The clinical outcomes included radiographic parameters of the forefoot, hindfoot, and ankle alignment, ankle activity, recurrent pain, and peri-operative complications., Results: After a mean follow-up of 23.17 ± 6.65 months, degenerative arthritis and prosthetic dislocation and other complications were not observed on plain radiographs. Each 3D-printed talar prosthesis was placed in the original anatomical position. The parameters which have significant changes pre-operative and post-operative are as follows: talar height, 27.59 ± 5.99 mm and 34.56 ± 3.54 mm (95% CI - 13.05 to - 0.87, t = 2.94, P = 0.032) and Meary's angle, 11.73 ± 4.79° and 4.45 ± 1.82° (95% CI 1.29~22.44, t = 2.89, P = 0.034). The AOFAS hindfoot score improved from 26.33 ± 6.62 to 79.67 ± 3.14 at the final follow-up (95% CI 43.36~63.30, t = 13.75, P = 0.000). The VAS score decreased from 6.33 ± 1.03 to 0.83 ± 0.75 (95% CI 4.40~6.60, t = 12.84, P = 0.000). The post-operative satisfaction scores regarding pain relief, activities of daily living, and return to recreational activities were good to excellent, and the change of activity range was statistically significant., Conclusions: The 3D printing patient-specific total talar prostheses allowed anatomical reconstruction in TNC. This novel treatment with 3D-printed prostheses could serve as a reliable patient-specific alternative in TNC., (© 2021. The Author(s).)

Object To examine the preliminary clinical efficacy of custom-made three-dimensional(3D) printed talus prosthesis in the treatment of collapse talus necrosis. Methods: The clinical data of 8 patients who received 3D printed custom-made talus prostheses replacement for severe collapsed necrosis of the talus at the Orthopaedic Sports Medical Center, the First Affiliated Hospital to Army Medical University were analyzed retrospectively.All patients were male,with an average age of 38.0 years (range:22 to 65 years).There were 5 cases of left talus collapse and 3 cases of right talus collapse,with the course of disease of 29.7 weeks (range:6 to 96 weeks).The CT data of contralateral healthy talus were used for mirror image design references for the prosthesis,and the electron-beam 3D printing technology was used to prepare the prosthesis.Titanium alloy (Ti6Al4V) was taken as the material for the preparation of the talus body prosthesis,and Co-Cr-Mo material was used as the material for the preparation of the tibialis talus lateral joint surface prosthesis,and the subtalar joint surface of the prosthesis was made from a microporous casting technique.The prosthesis was analyzed preoperatively by digital three-dimensional finite element analysis and solid comparison techniques to measure anatomic match of the prosthesis.A longitudinal incision on medial ankle was made.The necrotic talus was completely removed and the prosthesis was then implanted.The patient was reexamined in the outpatient department 3, 6, and 12 months after surgery.Primary outcome measures were the American Orthopaedic Foot and Ankle Society(AOFAS) ankle-hind foot score,visual analogue scale(VAS) and ankle range of motion.Changes in imaging data and plantar pressure were also assessed.Repeated measures analysis of variance and paired- t test were used to compare the data. Results: The talus prosthesis measure preoperatively was completely consistent with that contralateral healthy talus and there was no operation-related complication. All the wounds healed primarily. The patients were followed up effectively for 23.17 months (range:12 to 48 months).The preoperative dorsiflexion of patients was (7.6±5.7)°,it increased to(14.2±6.6)° at 12 month after surgery ( t =-2.67, P =0.03).The plantar flexion increased from (22.0±9.9)°preoperatively to (29.2±8.7)° at 12 month after surgery ( t =-8.95, P <0.01).Preoperative AOFAS ankle-hind foot score was 26.3±6.6,and it increased to 70.1±2.2,76.0±3.4 and 79.3±4.2 at 3 month,6 month and 12 month after surgery( F =56.81, P <0.01);Pre-operative VAS was[ M ( Q R )]3.0(0.8),and it increased to 2.5(1.0),1.5(1.0),1.0(1.0)at 3 month,6 month and 12 month after surgery( F =20.00, P <0.01).At the last follow-up,imaging reexamination showed that the prosthesis of all patients were in stable position with no sign of subsidence.No secondary ankle fusion or revision was required.The talus height increased from (27.6±6.0)mm preoperatively to (34.6±3.5)mm ( t =-2.94, P <0.01).The plantar pressure showed that the maximum pressure on the healthy ankle was(629.9±26.1)N,and that on the affected side was(521.4±14.4)N.The pressure on the healthy ankle was(350.6±29.6)N,and that on the necrotic side was (212.3±9.7)N.The load on the contralateral forefoot was(38.1±2.8)% and that on the necrotic side was(11.5±2.0)%.The load on the contralateral hindfoot was (24.6±2.5)% and that on the necrotic side was (21.1±1.8)%. Conclusions: The custom-made 3D printed talus prosthesis could restore the talus anatomy,recover the ankle joint function,relieve the pain of patients and improve the life quality of patients.The effect on plantar pressure is mainly achieved by adjusting the center of gravity of plantar pressure backwards and the increase of weight bearing of the healthy foot.