An oil-in-gel type of organohydrogel loaded with methylprednisolone for the treatment of secondary injuries following spinal cord traumas.

The secondary injuries following traumatic spinal cord injury (SCI) is a multiphasic and complex process that is difficult to treat. Although methylprednisolone (MP) is the only available pharmacological regime for SCI treatment, its efficacy remains controversial due to its very narrow therapeutic time window and safety concerns associated with high dosage. In this study, we have developed an oil-in-gel type of organohydrogel (OHG) in which the binary oleic-water phases coexist, for the local delivery of MP. This new OHG is fabricated by a glycol chitosan/oxidized hyaluronic acid hydrophilic network that is uniformly embedded with a biocompatible oil phase, and it can be effectively loaded with MP or other hydrophobic compounds. In addition to spatiotemporally control MP release, this biodegradable OHG also provides a brain tissue-mimicking scaffold that can promote tissue regeneration. OHG remarkably decreases the therapeutic dose of MP in animals and extends its treatment course over 21 d, thereby timely manipulating microglia/macrophages and their associated with signaling molecules to restore immune homeostasis, leading to a long-term functional improvement in a complete transection SCI rat model. Thus, this OHG represents a new type of gel for clinical treatment of secondary injuries in SCI.

Functional mechanism and clinical implications of LINC00339 in delayed fracture healing.

OBJECTIVE: Delayed fracture healing is a common complication of fractures that significantly impacts human health. This study aimed to explore the role of LINC00339 (lncRNA) in delayed fracture healing to provide new directions for its treatment. METHODS: This study included 82 patients with fractures healing in a normal manner and 90 patients experiencing delayed fracture healing. Levels of LINC00339, miR-16-5p, and osteogenic marker-related mRNAs were measured using RT-qPCR. The predictive potential of LINC00339 for delayed fracture healing was validated using ROC curve analysis. The interaction between LINC00339 and miR-16-5p was validated using dual-luciferase reporter assays and RIP experiments. CCK-8 was used to assess cell proliferation, and apoptosis rates were measured by flow cytometry. RESULTS: LINC00339 was significantly upregulated in delayed fracture healing patients and exhibited strong predictive ability for this condition. Overexpression of LINC00339 inhibited osteoblast proliferation, promoted apoptosis, and reduced mRNA levels of osteogenic markers (P < 0.05). miR-16-5p was recognized as a target mRNA of LINC00339, with LINC00339 exerting negative regulation on miR-16-5p, while overexpression of miR-16-5p mitigated the inhibitory effects of LINC00339 on fracture healing (P < 0.05). CONCLUSION: This research indicated that LINC00339 may serve as a diagnostic marker for delayed fracture healing and revealed the function of the LINC00339/miR-16-5p axis on fracture healing by regulating osteoblasts.

Multicenter integration analysis of TRP channels revealed potential mechanisms of immunosuppressive microenvironment activation and identified a machine learning-derived signature for improving outcomes in gliomas.

AIM: This study aimed to explore the mechanisms of transient receptor potential (TRP) channels on the immune microenvironment and develop a TRP-related signature for predicting prognosis, immunotherapy response, and drug sensitivity in gliomas. METHODS: Based on the unsupervised clustering algorithm, we identified novel TRP channel clusters and investigated their biological function, immune microenvironment, and genomic heterogeneity. In vitro and in vivo experiments revealed the association between TRPV2 and macrophages. Subsequently, based on 96 machine learning algorithms and six independent glioma cohorts, we constructed a machine learning-based TRP channel signature (MLTS). The performance of the MLTS in predicting prognosis, immunotherapy response, and drug sensitivity was evaluated. RESULTS: Patients with high expression levels of TRP channel genes had worse prognoses, higher tumor mutation burden, and more activated immunosuppressive microenvironment. Meanwhile, TRPV2 was identified as the most essential regulator in TRP channels. TRPV2 activation could promote macrophages migration toward malignant cells and alleviate glioma prognosis. Furthermore, MLTS could work independently of common clinical features and present stable and superior prediction performance. CONCLUSION: This study investigated the comprehensive effect of TRP channel genes in gliomas and provided a promising tool for designing effective, precise treatment strategies.

D-mannose alleviates intervertebral disc degeneration through glutamine metabolism.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.

Clinical characteristics and prognostic analysis of metachronous bilateral breast carcinoma: a retrospective study based on propensity score matching.

BACKGROUND: To investigate clinical characteristics, treatment, outcomes, and prognostic risk factors of metachronous bilateral breast carcinoma (MBBC) and provide a theoretical basis for clinical management of MBBC. METHODS: This was a retrospective study. From January 1, 2010 to March 31, 2022, a total of 23,010 patients with breast cancer underwent surgical treatment at the Breast Center of the Fourth Hospital of Hebei Medical University, including 386 patients with MBBC. Propensity score matching (PSM) was performed on MBBC patients and unilateral breast cancer (UBC) patients in a 1:1 ratio, and 210 UBC patients and 210 MBBC patients were finally matched. Clinical medical records of all patients were collected, including age of onset, family history of breast cancer, tumor size, lymph node status, TNM stage, mode of surgery, menstruation, pathological type, immunohistochemical (IHC) typing, treatment, disease-free survival (DFS), and overall survival (OS). RESULTS: The result showed that age of onset of the second primary cancer (SPC) was significantly older than that of the first primary cancer (FPC) (P = 0.024). Baseline data from MPPC patients showed that the tumor size of FPC was significantly larger than that of SPC (P = 0.043), and the proportion of PR ( +) in FPC is significantly higher than that in SPC (P = 0.045). Among MBBC patients with FPC for estrogen receptor (ER) or progesterone receptor (PR) ( +) and Her-2 (-), clinical characteristics and treatment results showed that the proportion of PR ( +) in the drug-resistant group was significantly lower than that in the non-drug-resistant group. The 2-year OS rate of SPC in the drug-resistant group was significantly shorter than those of the non-drug-resistant group (78.9% vs 100%, P < 0.05). The result of PSM-based comparison between MBBC patients and UBC patients showed significantly lower proportion of MBBC patients with SPC received chemotherapy compared to UBC patients (P = 0.026), and there was no significant difference in OS and DFS between SPC course of MBBC patients and UBC patients (P > 0.05). The univariate analysis showed that high TNM stage was a risk factor for death and disease progression in MBBC patients, with the risk of death in stage III MBBC patients being about 5 times higher than that in stage I MBBC patients (HR = 4.97, 95%CI = 1.42-17.31, P = 0.012), and the risk of disease recurrence being about 3.5 times higher than that in stage I MBBC patients (HR = 3.55, 95%CI = 1.07-11.81, P = 0.039). CONCLUSION: In summary, this study presented clinical characteristics, treatment options, and outcomes of MBBC patients and patients with MBBC who were resistant to endocrine therapy have a worse SPC survival prognosis. The course of SPC in MBBC patients was similar to that of UBC in terms of prognosis and survival, which suggested that SPC can be treated according to UBC treatment regimen. High TNM stage was a prognostic risk factor for SPC patients.

Bibliometric analysis of the gut microbiota and stroke from 2002 to 2022.

Stroke is the fifth leading cause of death worldwide, and the functional status of the gut plays a key role in patients' prognosis. Recent publications have explored the gut association with stroke, but few articles have been published that specifically address a comprehensive bibliometric analysis of the gut microbiota and its association with stroke. To address this gap, we used bibliometric methods to examine the landscape of research concerning the gut and stroke over approximately two decades, utilizing the Web of Science Core Collection (WoSCC). On November 1, 2022, a search was conducted for English-language articles published between 2002 and 2022, with only including original articles. Visual and statistical analyses were performed using CiteSpace, VOSviewer, and Bibliometrix 4.1.0 Package. After screening relevant articles, the results revealed that the number of articles published in this field has progressively increased during the last two decades. In particular, the total number of publications rapidly increased year by year from 2014. Among them, China ranked first in the world with a total of 227 publications. Authorship analysis highlighted Wang Z as the most prolific author, with 18 publications and an H-index of 14, highlighting significant contributions to this field. Meanwhile, the Southern Medical University of China was identified as the most productive institution. Moreover, analysis of keywords revealed that 'cerebral ischemia', 'intestinal microbiota', 'gut microbiota', and 'trimethylamine N-oxide' were popular topics searched, and research on the relationship between stroke and the gut continues to be a research hotspot. In summary, this study presents an overview of the progress and emerging trends in research on the relationship between stroke and gut health over the past two decades, providing a valuable resource for researchers aiming to understand the current state of the field and identify potential directions for future studies.

Effect of Diabetes on Wound Healing: A Bibliometrics and Visual Analysis.

Objective: The quality of life of diabetic patients is seriously affected by wound healing difficulty, which can lead to increased infection, skin deep tissue injury and continuous pain. By analyzing the research trends and hot spots in this field, the visualization analysis map is constructed. Methods: The contents of the selected articles were sorted out and analyzed by bibliometrics. We use CiteSpace, Vosviewer and HistCite to visualize literature information, including national publication statistics, institutions, authors, journal partnerships, and citations of published articles. Results: Among the 2942 articles, the United States and China ranked first in both article circulation and TGCS, and many countries also cooperated. The collaboration between schools and research institutions is a core part of dissertation research institution collaboration, with most authors coming from the same institution. Most of the literature studies on the mechanisms and methods of promoting diabetic wound healing. Improving cell function or making innovative attempts in local treatment are the fruits of researchers' efforts to promote diabetic wound healing in recent years. Conclusion: Through the metrology method, the time distribution, author institution, cooperation network, research status, research hotspot and development trend of the literature on the influence of diabetes on wound healing were intuitively displayed, which provided a reference for further research and development direction.

Enhancement of Nutrient Composition and Non-Volatile Flavor Substances in Muscle Tissue of Red Drum (Sciaenops ocellatus) Through Inland Low Salinity Saline-Alkaline Water Culture.

The red drum (Sciaenops ocellatus), a globally significant marine aquaculture species, boasts formidable osmoregulatory capabilities and remarkable adaptability to low salinity, making it an ideal candidate for commercial cultivation in inland low salinity saline-alkaline waters. However, studies on the fundamental nutritional composition and flavor quality of S. ocellatus in these inland low salinity saline-alkaline waters remain unreported. This study delves into the impact of inland low salinity saline-alkaline environments on the basic nutritional components and nonvolatile flavor substances (including free amino acids and free nucleotides) in the muscle tissue of S. ocellatus. The findings reveal that redfish cultivated in these conditions exhibit a significant increase in the crude fat, ash, and protein content in their dorsal muscle tissue, coupled with a decrease in moisture content (p < 0.05), indicating an enhancement in the nutritional value of the dorsal muscle tissue. Furthermore, this cultivation environment significantly elevates the content of free amino acids in the muscle tissue (p < 0.05), particularly those contributing to umami and sweet tastes, while reducing the relative content of bitter amino acids. Although the total content of free nucleotides decreased, the equivalent umami concentration (EUC) in the muscle tissue markedly increased (p < 0.05) due to the synergistic effect of umami amino acids and flavor nucleotides, enhancing the umami taste characteristics. Therefore, inland low salinity saline-alkaline aquaculture not only elevates the nutritional value of S. ocellatus muscle tissue but also improves its umami flavor characteristics. This discovery opens new perspectives for further research into the impact of inland low salinity saline-alkaline environments on the flavor properties of marine animals.

Shrimp Cultured in Low-Salt Saline-Alkali Water has a Better Amino Acid Nutrition and Umami─Comparison of Flavors between Saline-Alkali Water- and Seawater-Cultured Litopenaeus vannamei.

The advantages of Litopenaeus vannamei farming in saline-alkali water have gradually attracted attention, but few studies have focused on its flavor. In this study, L. vannamei cultured in saline-alkali water (SS) and ordinary seawater (CS) (both have a breeding time of 120 days) were selected for analysis (n = 5). High-performance liquid chromatography (HPLC) was used to measure free amino acids and flavoring nucleotides in the muscles of L. vannamei, while the taste activity value (TAV) and equivalent umami concentration (EUC) were used to analyze the degree of umami. The total essential amino acids (TEAA) in the SS group were 238.41 ± 46.24 mg/mL, significantly higher than that in the CS group (107.06 ± 15.65 mg/mL). The total amount of flavor nucleotides in the SS group was 2948.51 ± 233.66 µg/mL, significantly higher than those in the CS group (2530.37 ± 114.67 µg/mL). The content and TAV of some free amino acids (Glu, Cys-s) in the SS group were significantly higher. Meanwhile, due to the significant increase in IMP, the synergistic effect of free amino acids and flavored nucleotides leads to higher EUC. The significant separation of SS and CS samples in principal component analysis (PCA) indicates a significant difference between the two groups. Our results indicate that shrimp cultured in saline-alkali water has a stronger umami. This study enriches the basic theories related to the flavor of salt-alkali water crustaceans.

A Time Mode Pulse Interleaver in a Silicon-on-Insulator Platform for Optical Analog-to-Digital Converters.

We propose and demonstrate a novel on-chip optical sampling pulse interleaver based on time mode interleaving. The designed pulse interleaver was fabricated on a 220 nm silicon-on-insulator (SOI) platform, utilizing only one S-shaped delay waveguide. Interleaving is achieved by the relative time delay between different optical modes in the waveguide, eliminating the need for any active tuning. The total length of the delay waveguide is 5620.5 µm, which is reduced by a factor of 46.3% compared with previously reported time-wavelength interleaver schemes. The experimental results indicate that the device can convert an optical pulse into a 40 GHz pulse sequence composed of four pulses with a root mean square (RMS) timing error of 0.9 ps, making it well suited for generating high-frequency sampling pulses for optical analog-to-digital converters.

miR-30d-5p inhibits proliferation, invasion and migration of breast cancer cells by targeting SERPINE1 and promoting fatty acid ß-oxidation.

Breast cancer (BC) is among the top three most prevalent cancers across the world, especially in women, and its pathogenesis is still unknown. Fatty acid ß-oxidation is highly associated with breast cancer. Serpin family E member 1 (SERPINE1)-induced down-regulation of fatty acid ß-oxidation can facilitate BC cell proliferation, invasion, and metastasis. In this paper, the difference of miR-30d-5p expressions in both cancerous tissues and para-carcinoma tissues was first detected. Next, the expressions of SERPINE1, long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) in the aforementioned tissues were analyzed. Finally, miR-30d-5p mimics were supplemented to breast cancer cells to observe the miR-30d-5p effect upon breast cancer cells. Via immunofluorescence assay and Western blotting, it was found that cancerous tissues had lower expressions of miR-30d-5p, MCAD and LCAD and a higher expression of SERPINE1 than para-carcinoma tissues. The miR-30d-5p mimic group had a decreased SERPINE1 expression and increased MCAD and LCAD expressions compared with the NC group, thus inhibiting BC cell proliferation, invasion, and metastasis. To sum up, miR-30d-5p blocks the cell proliferation, invasion and metastasis by targeting SERPINE1 and promoting fatty acid ß-oxidation. Preclinical studies are further required to establish a fatty acid ß-oxidation-targeting therapy for breast cancer.

Recent advances in combatting bacterial infections via well-designed metallacycles/metallacages.

Bacterial infections can lead to the development of large-scale outbreaks of diseases that pose a serious threat to human life and health. Also, conventional antibiotics are prone to producing resistance and allergic reactions, and their therapeutic effect is dramatically diminished when bacterial communities form biofilms. Fortunately, well-designed supramolecular coordination complexes (SCCs) have been used as antibacterials or anti-biofilms in recent years. SCCs can kill bacteria by directly engaging with the bacterial surface through electrostatic interactions or by penetrating the bacterial membrane through the auxiliary effect of cell-penetrating peptides. Furthermore, scientists have engineered fluorescent SCCs that can produce reactive oxygen species (ROS) to eliminate bacteria when exposed to laser irradiation, and they also demonstrate outstanding performance in in vivo imaging, enabling integrated diagnosis and treatment. In this review, we summarize the design strategy and applications of SCCs in antibacterials or anti-biofilms and provide an outlook on future research.

Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway.

AIMS: The crosstalk between ferroptosis and neuroinflammation considerably impacts the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Neutral polysaccharide from Gastrodia elata (NPGE) has shown significant effects against oxidative stress and inflammation. This study investigated the potential effects of NPGE on CIRI neuropathology. METHODS: The effects of NPGE were studied in a mouse model of ischemic stroke (IS) and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells. RESULTS: NPGE treatment decreased neurological deficits, reduced infarct volume, and alleviated cerebral edema in IS mice, and promoted the survival of OGD/R-induced HT22 cells. Mechanistically, NPGE treatment alleviated neuronal ferroptosis by upregulating GPX4 levels, lowering reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ excessive hoarding, and meliorating GSH levels and SOD activity. Additionally, it inhibited neuroinflammation by down-regulating the level of IL-1ß, IL-6, TNF-α, NLRP3, and HMGB1. Meanwhile, NPGE treatment alleviated ferroptosis and inflammation in erastin-stimulated HT22 cells. Furthermore, NPGE up-regulated the expression of NRF2 and HO-1 and promoted the translocation of NRF2 into the nucleus. Using the NRF2 inhibitor brusatol, we verified that NRF2/HO-1 signaling mediated the anti-ferroptotic and anti-inflammatory properties of NPGE. CONCLUSION: Collectively, our results demonstrate the protective effects of NPGE and highlight its therapeutic potential as a drug component for CIRI treatment.

APOBEC3C is a novel target for the immune treatment of lower-grade gliomas.

BACKGROUND: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs. METHODS: The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C. RESULTS: A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage. CONCLUSIONS: A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival.Abbreviation: A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma.

CAR-T treatment for cancer: prospects and challenges.

Chimeric antigen receptor (CAR-T) cell therapy has been widely used in hematological malignancies and has achieved remarkable results, but its long-term efficacy in solid tumors is greatly limited by factors such as the tumor microenvironment (TME). In this paper, we discuss the latest research and future views on CAR-T cell cancer immunotherapy, compare the different characteristics of traditional immunotherapy and CAR-T cell therapy, introduce the latest progress in CAR-T cell immunotherapy, and analyze the obstacles that hinder the efficacy of CAR-T cell therapy, including immunosuppressive factors, metabolic energy deficiency, and physical barriers. We then further discuss the latest therapeutic strategies to overcome these barriers, as well as management decisions regarding the possible safety issues of CAR-T cell therapy, to facilitate solutions to the limited use of CAR-T immunotherapy.

An exploratory study of delayed flash visual evoked potential P2 wave latency in subcortical arteriosclerotic encephalopathy.

BACKGROUND: Patients with cognitive dysfunction may present with significantly prolonged the P2 wave latency of flash visual evoked potential. However, no studies have been reported on whether the P2 wave latency of flash visual evoked potential is prolonged in patients with subcortical arteriosclerotic encephalopathy (SAE). OBJECTIVE: To examine the relationship between flash visual evoked potential P2 wave latency (FVEP-P2 wave latency) and cognitive impairment in patients with SAE. METHODS: Overall, we recruited 38 SAE patients as the observation cohort (OC) and 34 healthy volunteers as the control cohort (CC). We measured the FVEP-P2 wave latency for both groups. The SAE patients' cognitive abilities were evaluated via mini-mental state examination (MMSE) and the association between the latency of FVEP-P2 and MMSE score was explored by Pearsons´s correlation test. RESULTS: There is no significant difference between OC (21 males and 17 females; 68.6 ± 6.7 years of age and 9.6 ± 2.8 years of education) and CC (19 males and 15 females; 65.3 ± 5.9 years of age and 10.1 ± 2.6 years of education) in gender and age composition and education level. The FVEP-P2 wave latency of the CC group was (108.80 ± 16.70) ms and the OC FVEP-P2 wave latency was (152.31 ± 20.70) ms. The OC FVEP-P2 wave latency was significantly longer than the CC (P < 0.05). In terms of MMSE scores, the MMSE scores of CC was (28.41 ± 2.34), and that of OC was (9.08 ± 4.39). Compared to the CC, the OC MMSE score was significantly lower (P < 0.05). In addition, the FVEP-P2 wave latency was inversely related to the MMSE (r = -0.4465, P < 0.05) in SAE patients. CONCLUSION: The FVEP-P2 wave latency wave latency was significantly prolonged in SAE patients and strongly associated with the degree of cognitive dysfunction.

Effect of Domestication on Nonvolatile Flavor Substances in Mud Crabs (Scylla paramamosain): A Way to Improve the Quality of Commercial Crabs.

In this study, the best domestication time for mud crabs (Scylla paramamosain) that were domesticated in the same region was explored. MC crabs (Mang Cai City, Vietnam), TS crabs (Taishan City, Guangdong Province, China), and NB crabs (Ningbo City, Zhejiang Province, China) were used as experiment groups, which were all domesticated in the Sanmen area for 28 days. Then, free amino acids and flavor nucleotides in muscles and hepatopancreas were determined. In MC and NB crabs, flavor amino acids in hepatopancreas and equivalent umami concentration (EUC) of flavor nucleotides in the hepatopancreas and muscles were lower than those of CK1 and CK3 crabs before domestication (0 day). There was no significant difference between MC and CK1 and between NB and CK3 crabs after 28 days of domestication. The content of umami amino acids, the total content of flavor nucleotides, and EUC in the hepatopancreas in TS crabs were lower than those in CK2 crabs and were still lower than those in CK2 crabs after 28 days of domestication. Therefore, it takes at least a month to domesticate mud crabs. The theoretical basis and technical reference for the directional cultivation of the flavor quality of mud crabs were provided in this study..

Correlation between the rate of morphological changes and rupture of intracranial aneurysms during one cardiac cycle analyzed by 4D-CTA.

Objective: This study aimed to analyze the relationship between the rate of morphological changes and intracranial aneurysm rupture during the cardiac cycle. Methods: Eighty-four patients with intracranial aneurysms were retrospectively analyzed and divided into the rupture (42 cases) and unruptured (42 cases) groups. Four-dimensional computed tomography angiography (4D-CTA) was performed to collect quantitative parameters of aneurysm morphology and calculate the morphological change rate. The potential factors associated with aneurysm rupture were determined by comparing the general clinical data and rate of change in the location and morphology of the aneurysm between the two groups. Results: Each morphological change rate in the rupture group was generally higher than that of the unruptured group. The rate of dome height change and aneurysm volume change were independent factors associated with aneurysm rupture. ROC curve analysis revealed that the diagnostic accuracy of the aneurysm volume change rate was higher. When the volume change rate was 12.33%, the sensitivity and specificity of rupture were 90.5 and 55.8%, respectively. Conclusion: The rate of change in dome height and volume of intracranial aneurysms during one cardiac cycle were independent factors associated with aneurysm rupture.

Characterizing polyproline II conformational change of collagen superhelix unit on adsorption on gold surface.

The dynamic process of protein binding onto a metal surface is a frequent occurrence as gold nanoparticles are increasingly being used in biomedical applications, including wound treatment and drug transport. Collagen, as a major component of the extracellular matrix, has potentially advantageous biomedical applications, due to its excellent biocompatibility and elasticity properties. Therefore, a mechanistic comprehension of how and which species in collagen interact with gold nanoparticles is a prerequisite for collagen-gold complexes in clinical application. However, the dynamic behavior of collagen with the polyproline II (PPII) conformation on gold sheets at the molecular level is too complex to capture under current experimental conditions. Here, using molecular dynamics simulations, we investigate the adsorption process and conformational behavior of the tripeptide Gly-Pro-Hyp with the repetitive unit of the collagen superhelix on the gold surface as a function of number of repeating units from 1 to 10. The different numbers of repeating units all prefer to approach the gold surface and adsorb via charged residues at the C-terminal or N-terminal ends, tending to form arch structures on the gold surface. Compared with the various tripeptide units in solution still retaining the native PPII conformation, the presence of the gold surface affects the formation of hydrogen bonds between the protein and water molecules, thus disrupting the PPII conformation of collagen. Specifically, the interaction between the gold surface and HYP limits the rotation of the dihedral angle of collagen, resulting in a tendency for the PPII conformation of the gold surface to transform to the ß-sheet conformation. The results provide an indication of how to improve the interaction between the terminal groups and the gold surface for the design of a bioavailable protein-gold material for medicinal purposes.

The shared microbiome in mud crab (Scylla paramamosain) of Sanmen Bay, China: core gut microbiome.

Introduction: The mud crab, Scylla paramamosain, holds great commercial significance as a marine crustacean widely cultivated in the Indo-Pacific region. Understanding the core gut microbiota of aquatic animals is crucial for their overall health and growth, yet the core gut microbiota of mud crab remains poorly characterized. Methods: In this study, we gathered gut samples from mud crabs across five locations within Sanmen Bay, China. Through the utilization of high-throughput sequencing, we delved into the composition of the gut microbial community and identified the core gut microbiome of mud crab. Results: Our results demonstrate that the gut microbial diversity of mud crab did not exhibit significant variation among the five sampling sites, although there were some differences in community richness. At the phylum level, we identified 35 representative phyla, with Firmicutes, Proteobacteria, Bacteroidota, and Campilobacterota as the dominant phyla. Among the 815 representative genera, we discovered 19 core genera, which accounted for 65.45% of the total sequences. These core genera were distributed across 6 phyla, and among them, Photobacterium exhibited the highest average relative abundance. Discussion: Photobacterium has probiotic activity and may play a crucial role in enhancing the immune response of the host and maintaining the diversity of the gut microbiota. Moreover, we observed a positive correlation between the relative abundance of core genera and the stability of the gut microbial community. Furthermore, our findings revealed distinct differences in gut microbial composition and specific taxa between the sexes of mud crab. These differences subsequently influenced the functionality of the gut microbial community. Overall, our investigation sheds light on the core gut microbiota of mud crab, emphasizing the importance of core gut microbial communities in maintaining the health and growth of these commercially significant marine crustaceans.