A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR-Light Triggered Hyperthermia.

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mngel) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG-Mngel with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

Boosting the Curie temperature of GaN monolayer through van der Waals heterostructures.

The pursuit of van der Waals (vdW) heterostructures with high Curie temperature and strong perpendicular magnetic anisotropy (PMA) is vital to the advancement of next generation spintronic devices. First-principles calculations are used to study the electronic structures and magnetic characteristics of GaN/VS2vdW heterostructure under biaxial strain and electrostatic doping. Our findings show that a ferromagnetic ground state with a remarkable Curie temperature (477 K), much above room temperature, exists in GaN/VS2vdW heterostructure and 100% spin polarization efficiency. Additionally, GaN/VS2vdW heterostructure still maintains PMA under biaxial strain, which is indispensable for high-density information storage. We further explore the electron, magnetic, and transport properties of VS2/GaN/VS2vdW sandwich heterostructure, where the magnetoresistivity can reach as high as 40%. Our research indicates that the heterostructure constructed by combining the ferromagnet VS2and the non-magnetic semiconductor GaN is a promising material for vdW spin valve devices at room temperature.

Genetic prediction of causal association between serum bilirubin and hematologic malignancies: a two-sample Mendelian randomized and bioinformatics study.

Introduction: An increasing number of cohort studies have shown a correlation between serum bilirubin and tumors, but no definitive causal relationship has been established between serum bilirubin and hematological malignancies.Therefore, the aim of the present study was to assess the causal relationship of serum bilirubin, including total bilirubin (TBIL) and direct bilirubin (DBIL), with hematological malignancies, including leukemia, lymphoma, and myeloma. Methods: We used a genome-wide association study (GWAS) collection of TBIL, DBIL, and hematological malignancies data. Using two-sample Mendelian randomization(MR), we assessed the impact of TBIL and DBIL on hematological malignancies. For this study, the inverse variance weighting method (IVW) was the primary method of MR analysis. In the sensitivity analysis, the weighted median method, MR Egger regression, and MR-PRESSO test were used. To understand the mechanisms behind TBIL and DBIL, we used three different approaches based on screening single nucleotide polymorphisms (SNPs) and their associated genes, followed by bioinformatics analysis. Results: The IVW test results showed evidence of effects of TBIL (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.58-12.62) and DBIL (OR: 3.31, 95% CI: 1.08-10.18) on the risk of acute myeloid leukemia (AML).The findings from bioinformatics indicated that TBIL could potentially undergo xenobiotic metabolism through cytochrome P450 and contribute to chemical carcinogenesis. Discussion: In this study, two-sample MR analysis revealed a causal relationship between TBIL, DBIL, and AML.

Superficial meningioma with bone involvement: surgical strategies and clinical outcomes.

INTRODUCTION: Meningiomas with bone involvement account for 4.5-17% of all intracranial meningiomas. Little is known about whether these meningiomas (WHO grade I) behave differently than meningiomas without bone involvement. We sought to study the relatively uncommon imaging manifestations of meningioma and to evaluate their clinical significance. METHODS: A single-institution retrospective cohort study of surgically treated superficial meningioma patients between 2011 and 2022 was conducted. Age, sex, preoperative imaging, operative data, and surgical outcomes were reviewed. Imaging variables and outcomes were reported for patients with bone-invading meningiomas and compared with those with nonbone-invading meningiomas. Univariate analyses were also conducted. RESULTS: Of 577 total superficial meningiomas treated surgically, 47 (8.1%) exhibited bone invasion. Most bone-invading meningiomas were parasagittal (n = 29, 61.7%). A total of 12.7% (n = 6) of patients with bone-invading meningioma had recurrence, whereas 9.1% (n = 48) of patients with non-bone-invading meningioma had recurrence (p = 0.426). No significant difference in the median time to recurrence was observed between patients with bone-invading meningiomas and patients with nonbone-invading meningiomas (69.8 months, Q1:53.1; Q3:81.4 months vs. 69.7 months, Q1:47.5; Q3:96.7; p = 0.638). CONCLUSIONS: Superficial meningioma with bone involvement had similar outcomes compared to those of superficial meningioma without bone involvement. Hyperostosis in meningioma (WHO grade I) may not be a surrogate for aggressive meningioma behavior.

Hemorrhagic cerebral venous infarction after vein injury during intraoperative lesion resection: incidence, hemorrhagic stages, risk factors and prognosis.

Objective: Cerebral venous infarction (CVI) after vein injury during intraoperative lesion resection is associated with intracranial hemorrhage. We conducted this study to identify the incidence, clinical and imaging features, and prognosis of hemorrhage CVI. Methods: We performed a retrospective analysis of patients with confirmed CVI after vein injury who underwent craniotomy in our hospital. Postoperative clinical symptoms were observed, and imaging features were compared between patients with and without intracranial hemorrhages through CT examination. Variables were analyzed using univariate and multivariate regression analyses. Results: Among 2,767 patients who underwent craniotomy, 93 cases of injured veins were identified intraoperatively. Hemorrhagic CVI was found in 38% (35/93). Multivariate analysis revealed that midline approach, meningioma, postoperative seizures, disorders of consciousness and interval in hours < 72 h were identified as predictors of hemorrhagic CVI. After 3 months of follow-up, the prognosis was poor in 15 cases (16%, 15/93), including death (two cases), vegetative survival (four cases), and severe disability (nine cases). Conclusions: Hemorrhagic CVI, as a critical complication after venous injury, can have disastrous consequences. Do not injure known veins intraoperatively. In case of injury, requisite remedial measures should be adopted during and after surgery.

Ecological niche shift and suitable area expansion of a globally invasive species Phthorimaea operculella.

Phthorimaea operculella is a major potato pest of global importance, early warning and detection of which are of significance. In this study, we analyzed the climate niche conservation of P. operculella during its invasion by comparing the overall climate niche from three dimensions, including the differences between native range (South America) and entire invaded region (excluding South America), the differences bwtween native range (South America) and five invaded continents (North America, Oceania, Asia, Africa, and Europe), as well as the differences between native region (South America) and an invaded region (China). We constructed ecological niche models for its native range (South America) and invaded region (China). The results showed that the climatic niche of the pest has expanded to varying degrees in different regions, indicating that the pest could well adapt to new environments during the invasion. Almost all areas of South America are suitable for P. operculella. In China, its suitable area is mainly concentrated in Shandong, Hebei, Tianjin, Beijing, Henan, Hubei, Yunnan, Guizhou, Sichuan, Hainan, northern Guangxi, southern Hunan, Anhui, Guangdong, Jiangsu, southern Shanxi, and southern Shaanxi. With increasing greenhouse gas emissions and global temperature, its suitable area will decrease at low latitude and increase gradually at high latitude. Specifically, the northern boundary will extend to Liaoning, Jilin, and the southeastern region of Inner Mongolia, while the western boundary extends to Sichuan and the southeast Qinghai-Tibet Plateau. The suitable area in the southeast Yunnan-Guizhou Plateau, Hainan Island, and the south of Yangtze River, will gradually decrease. The total suitable habitat area for P. operculella in China is projected to increase under future climate condition. From 2081 to 2100, under the three greenhouse gas emissions scenarios of ssp126, ssp370, and ssp585, the suitable area is expected to increase by 27.78, 165.54, and 140.41 hm2, respectively. Therefore, it is crucial to strengtehen vigilance and implement strict measures to prevent the further expansion of P. operculella.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Predictors of acute cerebellar bulge prior to posterior fossa lesion resection.

OBJECTIVE: A cerebellar bulge prior to posterior fossa resection is an emergency condition during surgery. Intraoperative cerebellar bulging not only increases the difficulty of lesion resection but also brings additional postoperative complications. Currently, there are few systematic reports on this topic. The predictors of cerebellar bulge and how to effectively prevent intraoperative cerebellar bulge are discussed in this article. METHODS: The clinical and imaging data of 527 patients with posterior fossa lesions who underwent resection at our hospital were retrospectively collected and analyzed. Perioperative clinical and imaging data were assessed. Variables were analyzed using univariate and multivariate regression analyses. RESULTS: Overall, 10.4% (55/527) of patients had intraoperative acute bulges. Multivariate analysis revealed that age <60 years, BMI ≥24, lesion size ≥30 (mm), cerebellar tonsillar herniation and/or hydrocephalus, and perilesional edema (moderate-severe) were predictors of cerebellar bulging. Relief of the cerebellar bulge can be accomplished by excising the lesion, releasing cerebrospinal fluid, and removing the cerebellum (the outer 1/3). Obvious cerebellar-related complications occurred in 4 patients postoperatively, and the symptoms disappeared after 6 months of follow-up. CONCLUSIONS: Cerebellar bulging during intraoperative posterior fossa resection deserves attention. Through the analysis of multiple factors related to cerebellar bulge, comprehensive evaluation and early intervention during the perioperative period are necessary. The incidence of cerebellar bulges can be reduced, and surgical complications related to cerebellar bulges can be avoided.

Protective effect of esculentoside A against myocardial infarction via targeting C-X-C motif chemokine receptor 2.

Myocardial infarction (MI) is the primary cause of cardiac mortality. Esculentoside A (EsA), a triterpenoid saponin, has anti-inflammatory and antioxidant activities. However, its effect on MI remains unknown. In this study, the protective effect and mechanisms of EsA against MI were investigated. EsA significantly alleviated hypoxia-induced HL-1 cell injury, including increasing cell viability, inhibiting reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) and lactate dehydrogenase (LDH) leakage. In mouse MI model by left coronary artery (LAD) ligating, EsA obviously restored serum levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI), superoxide dismutase (SOD) and malondialdehyde (MDA). In addition, the cardioprotective effect of EsA was further confirmed by infarct size, electrocardiogram and echocardiography. Mechanistically, the targeted binding relationship between EsA and C-X-C motif chemokine receptor 2 (CXCR2) was predicted by molecular docking and dynamics, and validated by small molecule pull-down and surface plasmon resonance tests. EsA inhibited CXCR2 level both in vitro and in vivo, correspondingly alleviated oxidative stress by suppressing NOX1 and NOX2 and relieved inflammation through inhibiting p65 and p-p65. It demonstrated that EsA could play a cardioprotective role by targeting CXCR2. However, the effect of EsA against MI was abolished in combination with CXCR2 overexpression both in vitro and in vivo. This study revealed that EsA showed excellent cardioprotective activities by targeting CXCR2 to alleviate oxidative stress and inflammation in MI. EsA may function as a novel CXCR2 inhibitor and a potent candidate for the prevention and intervention of MI in the future.

Strigolactones Might Regulate Ovule Development after Fertilization in Xanthoceras sorbifolium.

Strigolactones (SLs) were recently defined as a novel class of plant hormones that act as key regulators of diverse developmental processes and environmental responses. Much research has focused on SL biosynthesis and signaling in roots and shoots, but little is known about whether SLs are produced in early developing seeds and about their roles in ovule development after fertilization. This study revealed that the fertilized ovules and early developing pericarp in Xanthoceras sorbifolium produced minute amounts of two strigolactones: 5-deoxystrigol and strigol. Their content decreased in the plants with the addition of exogenous phosphate (Pi) compared to those without the Pi treatment. The exogenous application of an SL analog (GR24) and a specific inhibitor of SL biosynthesis (TIS108) affected early seed development and fruit set. In the Xanthoceras genome, we identified 69 potential homologs of genes involved in SL biological synthesis and signaling. Using RNA-seq to characterize the expression of these genes in the fertilized ovules, 37 genes were found to express differently in the fertilized ovules that were aborting compared to the normally developing ovules. A transcriptome analysis also revealed that in normally developing ovules after fertilization, 12 potential invertase genes were actively expressed. Hexoses (glucose and fructose) accumulated at high concentrations in normally developing ovules during syncytial endosperm development. In contrast, a low ratio of hexose and sucrose levels was detected in aborting ovules with a high strigolactone content. XsD14 virus-induced gene silencing (VIGS) increased the hexose content in fertilized ovules and induced the proliferation of endosperm free nuclei, thereby promoting early seed development and fruit set. We propose that the crosstalk between sugar and strigolactone signals may be an important part of a system that accurately regulates the abortion of ovules after fertilization. This study is useful for understanding the mechanisms underlying ovule abortion, which will serve as a guide for genetic or chemical approaches to promote seed yield in Xanthoceras.

Joint trajectory, transmission time and power optimization for multi-UAV data collecting system.

Unmanned aerial vehicles (UAVs) have been generally applied in the field of communication due to their small size, flexible mobility, and convenient deployment. As a mobile base station, the UAV node can quickly establish a line-of-sight link with the ground node, thereby improving communication performance. In this paper, we study a multi-UAV assisted data collecting system. Specifically, in the case of limited system energy consumption, UAV flight energy consumption and ground node data transmission energy consumption are considered as an general limitation, and considering the channel interference between nodes, a multi-UAV assisted data collection model is studied. An non-convex problem that maximizes the minimum amount of data collected from ground nodes is further formulated. Since the original optimization problem is non-convex that difficult to solve directly, the problem is first decomposed into four sub-problems, and then the solution of each sub-problem is obtained by using successive convex approximation and block coordinate descent method. Finally, based on the solution of the four subproblems, an iterative algorithm for joint optimization of data transmission planning, transmission power, UAV trajectory and mission time is proposed. Simulation experiments show that the proposed algorithm can obtain more transmission data than the baseline algorithms.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Eu3+-Doped Anionic Zinc-Based Organic Framework Ratio Fluorescence Sensing Platform: Supersensitive Visual Identification of Prescription Drugs.

Advanced techniques for both environmental and biological prescription drug monitoring are of ongoing interest. In this work, a fluorescent sensor based on an Eu3+-doped anionic zinc-based metal-organic framework (Eu3+@Zn-MOF) was constructed for rapid visual analysis of the prescription drug molecule demecycline (DEM), achieving both high sensitivity and selectivity. The ligand 2-amino-[1,1'-biphenyl]-4,4'-dicarboxylic acid (bpdc-NH2) not only provides stable cyan fluorescence (467 nm) for the framework through intramolecular charge transfer of bpdc-NH2 infinitesimal disturbanced by Zn2+ but also chelates Eu3+, resulting in red (617 nm) fluorescence. Through the synergy of photoinduced electron transfer and the antenna effect, a bidirectional response to DEM is achieved, enabling concentration quantification. The Eu3+@Zn-MOF platform exhibits a wide linear range (0.25-2.5 µM) to DEM and a detection limit (LOD) of 10.9 nM. Further, we integrated the DEM sensing platform into a paper-based system and utilized a smartphone for the visual detection of DEM in water samples and milk products, demonstrating the potential for large-scale, low-cost utilization of the technology.

[Mechanism of Xinshubao Tablets in exerting anti-inflammatory, vasodilation, and cardioprotective effects based on network pharmacology].

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.

Toward Explainable Multiparty Learning: A Contrastive Knowledge Sharing Framework.

Multiparty learning provides solutions for training joint models with decentralized data under legal and practical constraints. However, traditional multiparty learning approaches are confronted with obstacles, such as system heterogeneity, statistical heterogeneity, and incentive design. Determining how to deal with these challenges and further improve the efficiency and performance of multiparty learning has become an urgent problem to be solved. In this article, we propose a novel contrastive multiparty learning framework for knowledge refinement and sharing with an accountable incentive mechanism. Since the existing parameter averaging method is contradictory to the learning paradigm of neural networks, we simulate the process of human cognition and communication and analogize multiparty learning as a many-to-one knowledge-sharing problem. The approach is capable of integrating the acquired explicit knowledge of each client in a transparent manner without privacy disclosure, and it reduces the dependence on data distribution and communication environments. The proposed scheme achieves significant improvement in model performance in a variety of scenarios, as we demonstrated through experiments on several real-world datasets.

Efficacy and safety of epidural block with lidocaine for refractory severe plaque psoriasis: An open-label pilot study in real world setting.

Epidural block using lidocaine, a non-selective blocker of voltage-gated sodium channels (Nav), has demonstrated efficacy in the treatment of severe plaque psoriasis in a limited number of cases. This study aimed to evaluate the effectiveness and safety of epidural lidocaine block in adult patients with severe, treatment-resistant plaque psoriasis. This was an open-label pilot study. Patients with severe plaque-type psoriasis unresponsive to at least one systemic treatment were enrolled for a 1-week epidural lidocaine block and followed up for 48 weeks. Thirty-six patients participated, with 32 completing the study. At the 12-week mark, there was a remarkable 59% improvement in the mean Psoriasis Area Severity Index (PASI) score (P < 0.001). By week 48, 28 out of 32 patients (87%) achieved PASI 75, while 18 out of 32 (56%) reached PASI 90. Within 7 days, 20 out of 21 patients (95%) reported a reduction in itch, with a mean itch reduction of 82% at day 1 and 94% at day 7. Notably, no severe side effects were observed. Epidural lidocaine block proved to be an effective and safe long-term treatment option for individuals with refractory severe plaque psoriasis.

Histomorphological analysis of perfusion parameters and CNS lymphatic vessels in mice: an experimental method study.

To investigate the distribution and characteristics of lymphatic vessels within the central nervous system, we focus on the meninges of the spinal cord and brain parenchyma in mice. Additionally, we aim to provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels, while optimizing the perfusion parameters to improve histomorphological quality. Male C57BL/6J mice were randomly divided into four groups, with each group assigned a specific perfusion parameter based on perfusion volumes and temperatures. Immunofluorescence staining of lymphatics and blood vessels was performed on both meningeal and the brain tissue samples. Statistical analysis was performed using one-way analysis of variance to compare the groups, and a significant level of P < 0.05 was considered statistically significant. Our study reports the presence of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice. We highlight the crucial role of high perfusion volume of paraformaldehyde with low temperature in fixation for achieving optimal results. We provide experimental methods for obtaining optimal imaging and clear structures of lymphatic vessels in the meninges of the spinal cord and brain parenchyma in mice, which contribute to our understanding of the distribution and characteristics of lymphatic vessels within the central nervous system. Further research is warranted to explore the functional implications of these lymphatic vessels and their potential therapeutic significance in neurodegenerative and neuroinflammatory diseases.

The aging trajectories of brain functional hierarchy and its impact on cognition across the adult lifespan.

Introduction: The hierarchical network architecture of the human brain, pivotal to cognition and behavior, can be explored via gradient analysis using restingstate functional MRI data. Although it has been employed to understand brain development and disorders, the impact of aging on this hierarchical architecture and its link to cognitive decline remains elusive. Methods: This study utilized resting-state functional MRI data from 350 healthy adults (aged 20-85) to investigate the functional hierarchical network using connectome gradient analysis with a cross-age sliding window approach. Gradient-related metrics were estimated and correlated with age to evaluate trajectory of gradient changes across lifespan. Results: The principal gradient (unimodal-to-transmodal) demonstrated a significant non-linear relationship with age, whereas the secondary gradient (visual-to-somatomotor) showed a simple linear decreasing pattern. Among the principal gradient, significant age-related changes were observed in the somatomotor, dorsal attention, limbic and default mode networks. The changes in the gradient scores of both the somatomotor and frontal-parietal networks were associated with greater working memory and visuospatial ability. Gender differences were found in global gradient metrics and gradient scores of somatomotor and default mode networks in the principal gradient, with no interaction with age effect. Discussion: Our study delves into the aging trajectories of functional connectome gradient and its cognitive impact across the adult lifespan, providing insights for future research into the biological underpinnings of brain function and pathological models of atypical aging processes.

[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

Organic-inorganic composite hydrogels: compositions, properties, and applications in regenerative medicine.

Hydrogels, formed from crosslinked hydrophilic macromolecules, provide a three-dimensional microenvironment that mimics the extracellular matrix. They served as scaffold materials in regenerative medicine with an ever-growing demand. However, hydrogels composed of only organic components may not fully meet the performance and functionalization requirements for various tissue defects. Composite hydrogels, containing inorganic components, have attracted tremendous attention due to their unique compositions and properties. Rigid inorganic particles, rods, fibers, etc., can form organic-inorganic composite hydrogels through physical interaction and chemical bonding with polymer chains, which can not only adjust strength and modulus, but also act as carriers of bioactive components, enhancing the properties and biological functions of the composite hydrogels. Notably, incorporating environmental or stimulus-responsive inorganic particles imparts smartness to hydrogels, hence providing a flexible diagnostic platform for in vitro cell culture and in vivo tissue regeneration. In this review, we discuss and compare a set of materials currently used for developing organic-inorganic composite hydrogels, including the modification strategies for organic and inorganic components and their unique contributions to regenerative medicine. Specific emphasis is placed on the interactions between the organic or inorganic components and the biological functions introduced by the inorganic components. The advantages of these composite hydrogels indicate their potential to offer adaptable and intelligent therapeutic solutions for diverse tissue repair demands within the realm of regenerative medicine.