Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review.

Spatiotemporally controlled cargo release is a key advantage of nanocarriers in anti-tumor therapy. Various external or internal stimuli-responsive nanomedicines have been reported for their ability to increase drug levels at the diseased site and enhance therapeutic efficacy through a triggered release mechanism. Redox-manipulating nanocarriers, by exploiting the redox imbalances in tumor tissues, can achieve precise drug release, enhancing therapeutic efficacy while minimizing damage to healthy cells. As a typical redox-sensitive bond, the disulfide bond is considered a promising tool for designing tumor-specific, stimulus-responsive drug delivery systems (DDS). The intracellular redox imbalance caused by tumor microenvironment (TME) regulation has emerged as an appealing therapeutic target for cancer treatment. Sustained glutathione (GSH) depletion in the TME by redox-manipulating nanocarriers can exacerbate oxidative stress through the exchange of disulfide-thiol bonds, thereby enhancing the efficacy of ROS-based cancer therapy. Intriguingly, GSH depletion is simultaneously associated with glutathione peroxidase 4 (GPX4) inhibition and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization, triggering mechanisms such as ferroptosis and cuproptosis, which increase the sensitivity of tumor cells. Hence, in this review, we present a comprehensive summary of the advances in disulfide based redox-manipulating nanocarriers for anticancer drug delivery and provide an overview of some representative achievements for combinational therapy and theragnostic. The high concentration of GSH in the TME enables the engineering of redox-responsive nanocarriers for GSH-triggered on-demand drug delivery, which relies on the thiol-disulfide exchange reaction between GSH and disulfide-containing vehicles. Conversely, redox-manipulating nanocarriers can deplete GSH, thereby enhancing the efficacy of ROS-based treatment nanoplatforms. In brief, we summarize the up-to-date developments of the redox-manipulating nanocarriers for cancer therapy based on DDS and provide viewpoints for the establishment of more stringent anti-tumor nanoplatform.

Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

UniParser: Multi-Human Parsing With Unified Correlation Representation Learning.

Multi-human parsing is an image segmentation task necessitating both instance-level and fine-grained category-level information. However, prior research has typically processed these two types of information through distinct branch types and output formats, leading to inefficient and redundant frameworks. This paper introduces UniParser, which integrates instance-level and category-level representations in three key aspects: 1) we propose a unified correlation representation learning approach, allowing our network to learn instance and category features within the cosine space; 2) we unify the form of outputs of each modules as pixel-level results while supervising instance and category features using a homogeneous label accompanied by an auxiliary loss; and 3) we design a joint optimization procedure to fuse instance and category representations. By unifying instance-level and category-level output, UniParser circumvents manually designed post-processing techniques and surpasses state-of-the-art methods, achieving 49.3% AP on MHPv2.0 and 60.4% AP on CIHP. We have released our source code, pretrained models, and demos to facilitate future studies on https://github.com/cjm-sfw/Uniparser.

Comparative Study for Safety and Efficacy of OAGB and SADJB-SG: A Retrospective Study.

Purpose: Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures. Patients and Methods: Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures. Results: A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970±5.005 and 75.652±7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006±8.231 and 23.171±6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208±1508.220 yuan, which was significantly lower than the 57538.195±1374.994 yuan for SADJB-SG (P-value< 0.001). Conclusion: The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.

Vina-GPU 2.1: Towards Further Optimizing Docking Speed and Precision of AutoDock Vina and Its Derivatives.

AutoDock Vina and its derivatives have established themselves as a prevailing pipeline for virtual screening in contemporary drug discovery. Our Vina-GPU method leverages the parallel computing power of GPUs to accelerate AutoDock Vina, and Vina-GPU 2.0 further enhances the speed of AutoDock Vina and its derivatives. Given the prevalence of large virtual screens in modern drug discovery, the improvement of speed and accuracy in virtual screening has become a longstanding challenge. In this study, we propose Vina-GPU 2.1, aimed at enhancing the docking speed and precision of AutoDock Vina and its derivatives through the integration of novel algorithms to facilitate improved docking and virtual screening outcomes. Building upon the foundations laid by Vina-GPU 2.0, we introduce a novel algorithm, namely Reduced Iteration and Low Complexity BFGS (RILC-BFGS), designed to expedite the most time-consuming operation. Additionally, we implement grid cache optimization to further enhance the docking speed. Furthermore, we employ optimal strategies to individually optimize the structures of ligands, receptors, and binding pockets, thereby enhancing the docking precision. To assess the performance of Vina-GPU 2.1, we conduct extensive virtual screening experiments on three prominent targets, utilizing two fundamental compound libraries and seven docking tools. Our results demonstrate that Vina-GPU 2.1 achieves an average 4.97-fold acceleration in docking speed and an average 342% improvement in EF1% compared to Vina-GPU 2.0. The source code and tools for Vina-GPU 2.1 are freely available accompanied by comprehensive instructions and illustrative examples.

Nickel-Catalyzed Enantioselective Alkylation of Primary Phosphines.

Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis. The development of general and practical methods for the stereoselective construction of synthetically versatile P(III)-stereogenic phosphines is particularly appealing but remains elusive. Herein, we describe a nickel-catalyzed asymmetric alkylation of primary phosphines with alkyl halides for the synthesis of P-stereogenic secondary phosphine-boranes with high enantioselectivity and broad substrate scope. The resulting optically active secondary phosphine-boranes allow for further stereospecific transformations, thereby establishing a modular and efficient platform for the diversity-oriented construction of P-stereogenic phosphine compounds.

Three-dimensional chromatin mapping of sensory neurons reveals that promoter-enhancer looping is required for axonal regeneration.

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer-promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.

Colorimetric screening model for identification of menaquinone-7 (MK-7) producing strains.

In this study, a novel colorimetric screening method for identifying menaquinone-7 (MK-7) producing strains was established using potassium permanganate. To our knowledge, this method represents the first direct screening methodology for the identification of MK-7 producing strains. Utilizing this screening method, a new MK-7 producing strain, Bacillus subtilis GSA-184, was identified from the soil of the Tibetan Plateau. Under the optimized fermentation medium (50 g/L glycerol, 30 g/L yeast extract powder, 100 g/L soybean peptone, 1 g/L KH2PO4, and 1 g/L MnSO4), the production of MK-7 was increased to 25.7 mg/L. Additionally, the maximum production of MK-7 reached 36.46 mg/L after 48 h in a 5-L fermenter. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04097-1.

Development and validation of an MRI and clinicopathological factors prediction model for low anterior resection syndrome in anterior resection of middle and low rectal cancer.

Objective: To validate the predictive power of newly developed magnetic resonance (MR) morphological and clinicopathological risk models in predicting low anterior resection syndrome (LARS) 6 months after anterior resection of middle and low rectal cancer (MLRC). Methods: From May 2018 to January 2021, 236 patients with MLRC admitted to two hospitals (internal and external validation) were included. MR images, clinicopathological data, and LARS scores (LARSS) were collected. Tumor morphology data included longitudinal involvement length, maximum tumor diameter, proportion of tumor to circumference of the intestinal wall, tumor mesorectal infiltration depth, circumferential margin status, and distance between the tumor and anal margins. Pelvic measurements included anorectal angle, mesenterial volume (MRV), and pelvic volume. Univariate and multivariate logistic regression was used to obtain independent risk factors of LARS after anterior resection Then, the prediction model was constructed, expressed as a nomogram, and its internal and external validity was assessed using receiver operating characteristic curves. Results: The uni- and multivariate analysis revealed distance between the tumor and anal margins, MRV, pelvic volume, and body weight as significant independent risk factors for predicting LARS. From the nomogram, the area under the curve (AUC), sensitivity, and specificity were 0.835, 75.0 %, and 80.4 %, respectively. The AUC, sensitivity, and specificity in the external validation group were 0.874, 83.3 %, and 91.7 %, respectively. Conclusion: This study shows that MR imaging and clinicopathology presented by a nomogram can strongly predict LARSS, which can then individually predict LARS 6 months after anterior resection in patients with MLRC and facilitate clinical decision-making. Clinical relevance statement: We believe that our study makes a significant contribution to the literature. This method of predicting postoperative anorectal function by preoperative measurement of MRV provides a new tool for clinicians to study LARS.

New insights into the structure and function of microbial communities in Maxwell Bay, Antarctica.

The microbial communities inhabiting polar ecosystems, particularly in Maxwell Bay, Antarctica, play a pivotal role in nutrient cycling and ecosystem dynamics. However, the diversity of these microbial communities remains underexplored. In this study, we aim to address this gap by investigating the distribution, environmental drivers, and metabolic potential of microorganisms in Maxwell Bay. We analyzed the prokaryotic and eukaryotic microbiota at 11 stations, revealing distinctive community structures and diverse phylum dominance by using high-throughput sequencing. Spatial analysis revealed a significant impact of longitude on microbial communities, with microeukaryotes exhibiting greater sensitivity to spatial factors than microprokaryotes. We constructed co-occurrence networks to explore the stability of microbial communities, indicating the complexity and stability of microprokaryotic communities compared with those of microeukaryotes. Our findings suggest that the microeukaryotic communities in Maxwell Bay are more susceptible to disturbances. Additionally, this study revealed the spatial correlations between microbial communities, diversity, and environmental variables. Redundancy analysis highlighted the significance of pH and dissolved oxygen in shaping microprokaryotic and microeukaryotic communities, indicating the anthropogenic influence near the scientific research stations. Functional predictions using Tax4Fun2 and FUNGuild revealed the metabolic potential and trophic modes of the microprokaryotic and microeukaryotic communities, respectively. Finally, this study provides novel insights into the microbial ecology of Maxwell Bay, expanding the understanding of polar microbiomes and their responses to environmental factors.

Retrosynthetic analysis via deep learning to improve pilomatricoma diagnoses.

BACKGROUND: Pilomatricoma, a benign childhood skin tumor, presents diagnostic challenges due to its manifestation variations and requires surgical excision upon histological confirmation of its characteristic cellular features. Recent artificial intelligence (AI) advancements in pathology promise enhanced diagnostic accuracy and treatment approaches for this neoplasm. METHODS: We employed a multiscale transfer learning model, initiating the training process at high resolutions and adapting to broader scales. For evaluation purposes, we applied metrics such as accuracy, precision, recall, the F1 score, and the area under the receiver operating characteristic curve (AUROC) to measure the performance of the model, with the statistical significance of the results assessed via two-sided P tests. Our novel approach also included a retrosynthetic saliency mapping technique to achieve enhanced lesion visualization in whole-slide images (WSIs), supporting pathologists' diagnostic processes. RESULTS: Our model effectively navigated the challenges of global-scale classification, achieving a high validation accuracy of up to 0.973 despite some initial fluctuations. This method displayed excellent accuracy in terms of identifying basaloid and ghost cells, especially at lower scales, with slight variability in its ghost cell accuracy and more noticeable changes in the 'Other' category at higher scales. The consistent performance attained for basaloid cells was clear across all scales, whereas areas for improvement were identified in the 'Other' category. The model also excelled at generating detailed and interpretable saliency maps for lesion visualization purposes, thereby enhancing its value in digital pathology diagnostics. CONCLUSION: Our pilomatricoma study demonstrates the efficacy of a deep learning-based histopathological diagnosis model, as validated by its high performance across various scales, and it is enhanced by an innovative retrosynthetic approach for saliency mapping.

Increased Lymphatic Vessels: A Risk Factor for Severe Renal Function Loss in Obstructive Nephropathy Patients.

Background: Obstructive nephropathy (ON), resulting from hindered urine flow, significantly contributes to both acute kidney injury (AKI) and chronic kidney disease (CKD). Research has consistently highlighted increased lymphatic vessels (LVs) density in diverse kidney diseases. However, the precise involvement of LVs in ON remains unclear. Methods: Patients diagnosed with ON were enrolled in this study from January 2020 to December 2023. LVs and histological pathology in renal biopsy tissues were detected through immunohistochemistry and Periodic Acid-Schiff staining. Patients were categorized into two cohorts based on their estimated glomerular filtration rate (eGFR) levels: one cohort included patients with eGFR < 90, while the other encompassed those with eGFR ≥ 90. Univariate and multivariable logistic regression analyses were conducted to determine the odds ratio (OR) and 95% confidence interval (CI) for the association between the two cohorts. Results: 239 patients were enrolled in the study. The density of LVs was elevated in ON, with even higher densities observed in patients with severe renal impairment. Additionally, several risk factors contributing to the deterioration of renal function in ON patients have been identified, including age, ureteral calculi (UC), alanine aminotransferase (ALT), and uric acid (UA). Furthermore, by leveraging LVs density, multiple robust models have been established to predict severe renal impairment in ON. Conclusions: Lymphatic vessels density is significantly elevated in ON, serving as an independent risk factor for the decline in renal function.

How spousal cognitive functioning affects the level of depression in middle-aged and older adults: An instrumental variable study based on CHARLS in China.

A better understanding of the causal relationship between spousal cognitive functioning and depression levels among middle-aged and older adults is vital for effective health policymaking under the globally severe aging challenge. However, the related evidence is often limited by potential omitted-variable bias and reverse causation. This study uses an instrumental variables approach, namely the two-stage least squares (2SLS) method, to examine the impact of spousal cognitive functioning on depression levels among middle-aged and older adults in China. The data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) of 2020, including a total of 3,710 couples aged 45 years and above. Depression levels were measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10), while cognitive functioning was assessed using the Mini-Mental State Examination (MMSE). Spousal social participation was employed as the instrumental variable to address omitted-variable bias and reverse causation. Additionally, an interaction effect test between gender and spousal cognitive functioning was conducted. The results show that for each one-point increase in the spouse's MMSE score, the CES-D-10 score of middle-aged and older adults decreased by 17.1% to 68.2%. The OLS results indicated that women, rural residents, and middle-aged individuals were more sensitive to these changes. The interaction effect test results confirmed that women were more affected by changes in spousal cognitive functioning. However, after a more reliable 2SLS analysis, the results for age groups shifted, showing that middle-aged individuals were more sensitive to these changes, with a decrease in depression levels reaching 70.0%, compared to 60.2% for the elderly group. Nonetheless, given the prevalence of depression among the elderly, the impact of spousal cognitive decline on depression in this group should not be overlooked. Our findings highlight the importance of spousal cognitive health in managing depression among both middle-aged and older adults, with particular attention to women and rural populations.

Traditional Chinese Manual Therapy (Tuina) Improves Knee Osteoarthritis by Regulating Chondrocyte Autophagy and Apoptosis via the PI3K/AKT/mTOR Pathway: An in vivo Rat Experiment and Machine Learning Study.

Background: Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear. Objective: This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms. Methods: KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings. Results: Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1ß, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs. Conclusion: Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.

[Effects of ant nesting on seasonal dynamics of soil CH4 emissions in a tropical rubber-plantation forest]. / 蚂蚁筑巢对热带橡胶人工林土壤甲烷排放季节动态的影响.

Ant nests can affect the process and seasonal dynamics of forest soil methane emissions through mediating methane oxidation/reduction microorganisms and physicochemical environments. To explore the process and mechanism by which ant nests affect soil methane emissions from Hevea brasiliensis plantation in Xishuangbanna, we measured the seasonal dynamics of methane emissions from ant nest and non-nest soils by using static chamber-gas chromatography method, and analyzed the effect of ant nesting on the changes in functional microbial diversity, microhabitats, and soil nutrients in the plantations. The results showed that: 1) Ant nests significantly affected the mean annual soil methane emissions in tropical plantation. Methane emissions in ant nest were decreased by 59.9% than the non-nest soil. In the dry season, ant nest soil was a methane sink (-1.770 µg·m-2·h-1), which decreased by 87.2% compared with the non-nest soil, while it was a methane source (0.703 µg·m-2·h-1) that increased by 152.7% in the wet season. 2) Ant nesting affected methane emissions via changing soil temperature, humidity, carbon and nitrogen concentrations. In contrast to the control, the mean annual temperature, humidity, and carbon and nitrogen content increased by 4.9%-138.5% in ant nest soils, which explained 90.1%, 97.3%, 27.3%-90.0% of the variation in methane emissions, respectively. 3) Ant nesting affected the emission dynamics through changing the diversity and community structure of methane functional microbe. Compared with the control, the average annual methanogen diversity (Ace, Chao1, Shannon, and Simpson indices) in the ant nest ranged from -9.9% to 61.2%, which were higher than those (-8.7%-31.2%) of the methane-oxidising bacterial communities. The relative abundance fluctuations of methanogens and methanotrophic bacteria were 46.76% and -6.33%, respectively. The explaining rate of methanogen diversity to methane emissions (78.4%) was higher than that of oxidizing bacterial diversity (54.5%), the relative abundance explained by the dominant genus of methanogens was 68.9%. 4) The structural equation model showed that methanogen diversity, methanotroph diversity, and soil moisture were the main factors controlling methane emissions, contributing 95.6%, 95.0%, and 91.2% to the variations of emissions, respectively. The contribution (73.1%-87.7%) of soil temperature and carbon and nitrogen components to the emission dynamics was ranked the second. Our results suggest that ant nesting mediates the seasonal dynamics of soil methane emissions, primarily through changing the diversity of methane-function microorganisms and soil water conditions. The research results deepen the understanding of the mechanism of biological regulation of methane emission in tropical forest soil.

Virus-like Particles vaccine based on co-expression of G5 Porcine rotavirus VP2-VP6-VP7 induces a powerful immune protective response in mice.

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65 nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40 µg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

GelMA loaded with exosomes from human minor salivary gland organoids enhances wound healing by inducing macrophage polarization.

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action.

Etoposide, cisplatin, and sintilimab combined with anlotinib in successful treatment of adrenocortical carcinoma with lung metastasis: a case report.

Background: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC. Case presentation: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient's lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism. Conclusion: This case highlights the remarkable response of our patient's ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.

Hydration effect and molecular geometry conformation as critical factors affecting the longevity stability of G4-structure-based supramolecular hydrogels.

Nucleoside-derived supramolecular hydrogels based on G4-structures have been extensively developed in the biomedical sector and recognized for superior excellent biocompatibility and biodegradability. However, limited longevity and stability present a significant challenge. Chemical modifications in the molecular structure have been shown to enhance the longevity stability of G4-structure-based supramolecular hydrogels, but the precise way in which the molecular structure impacts the stability of the G4-structures and consequently affects the properties of the hydrogel remains to be elucidated. This issue represents a notable challenge in the field, which restricts their further applications to some extent. In this study, single crystals of Gd, αGd and αGd* were cultivated and compared with G. Notably, before this study, the single crystal structures of all natural nucleosides, with the exception of Gd, had been determined. The investigation into the molecular structure and supramolecular self-assembly properties of four guanosine analogs at the atomic scale revealed that the formation of G-quartets is critical for their ability to form hydrogels. The stability of the sugar ring geometry conformation (an intrinsic factor) and the disorder and strength of the hydration effect (extrinsic factors) are vital for maintaining the stability of the G4-structures. The rapid cooling changes the molecular geometry conformation, and the organic solvent changes the hydration effect, which can improve the longevity stability of G4-structure-based supramolecular hydrogels instead of chemical modifications. Consequently, the lifespan of the hydrogels was extended from 2 h to over one week. This advancement is expected to offer significant insights for future research in designing and developing G4-structure-based supramolecular hydrogels.

Extragastrointestinal stromal tumors with diffuse membranous distribution with bleeding: A case report.

BACKGROUND: Extragastrointestinal stromal tumors (EGIST) and gastrointestinal stromal tumors are of similar pathological type and form. Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity, the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors. CASE SUMMARY: The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days. Upon physical examination, the patient had flat and tough abdomen with mild pressing pain at lower abdomen, no obvious abdominal mass was touchable, and shifting dullness was positive. Positron emission tomography-computed tomography (CT) showed that in his peritoneal cavity, there were multiple nodules of various sizes, seroperitoneum, multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules. Plain CT scanning at epigastrium/hypogastrium/pelvic cavity + enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity, peritoneum and right groin. Tumor marker of carbohydrate antigen 125 was 808 U/mL, diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia, and postoperative pathological examination confirmed EGIST. Imatinib was administered with better therapeutic effect. CONCLUSION: Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation, and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.