Cytotoxic and Antibacterial Meroterpenoids Isolated from the Marine-Derived Fungus Talaromyces sp. M27416.

Three novel meroterpenoids, taladrimanins B-D (1-3), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds (4-6). We delineated taladrimanin B's (1) structure using HRESIMS and NMR, confirmed its configuration via quantum chemical NMR analysis and DP4+ methodology, and verified it through X-ray crystallography. ECD calculations determined the absolute configuration of compound 1, while comparative NMR and ECD analyses elucidated the absolute configurations of 2 and 3. These compounds are drimane-type meroterpenoids with a C10 polyketide unit (8R-configuration). We proposed a biosynthetic pathway and noted that compound 1 showed cytotoxic activity against MKN-45 and 5637 cell lines and selective antibacterial effects against Staphylococcus aureus CICC 10384.

Design of a novel gamma camera with large field of view for 16N diagnosis in the primary loop of nuclear reactor.

The assessment of the concentration and distribution of l6N, derived from 16O in the cooling water exposed to neutron irradiation, is essential for ensuring radiation safety during nuclear reactor operation. The imaging method allows for the visualization of the intensity distribution of these l6N by capturing gamma-rays emitted during their decay process. However, the existing gamma camera is exclusively compatible with gamma-rays below 2 MeV. In this paper, a novel gamma camera featuring a thick double-conical penumbra aperture, a pixelated Lu1.8Y0.2SiO5:Ce scintillator array, and a position-sensitive photomultiplier tube is proposed to address this limitation. This innovative design offers a large field of view (FOV) and is suitable for high energy extended gamma source imaging. The optimization of key parameters of the camera was conducted, and a FOV of 60° and an angular resolution of up to 4.57° were achieved. Imaging simulations, including a simplified model of the primary loop of the pressurized-water reactor by GEANT4 code and image reconstruction using the expectation maximum algorithm, demonstrated that the proposed gamma camera could obtain a satisfactory spatial resolution for diagnosing the distribution of 16N in the primary loop of a nuclear reactor.

A New Automated Prognostic Prediction Method Based on Multi-Sequence Magnetic Resonance Imaging for Hepatic Resection of Colorectal Cancer Liver Metastases.

Colorectal cancer is a prevalent and life-threatening disease, where colorectal cancer liver metastasis (CRLM) exhibits the highest mortality rate. Currently, surgery stands as the most effective curative option for eligible patients. However, due to the insufficient performance of traditional methods and the lack of multi-modality MRI feature complementarity in existing deep learning methods, the prognosis of CRLM surgical resection has not been fully explored. This paper proposes a new method, multi-modal guided complementary network (MGCNet), which employs multi-sequence MRI to predict 1-year recurrence and recurrence-free survival in patients after CRLM resection. In light of the complexity and redundancy of features in the liver region, we designed the multi-modal guided local feature fusion module to utilize the tumor features to guide the dynamic fusion of prognostically relevant local features within the liver. On the other hand, to solve the loss of spatial information during multi-sequence MRI fusion, the cross-modal complementary external attention module designed an external mask branch to establish inter-layer correlation. The results show that the model has accuracy (ACC) of 0.79, the area under the curve (AUC) of 0.84, C-Index of 0.73, and hazard ratio (HR) of 4.0, which is a significant improvement over state-of-the-art methods. Additionally, MGCNet exhibits good interpretability.

Field-Induced Transport Anisotropy in Single-Crystalline All-Inorganic Lead-Halide Perovskite Nanowires.

The dynamic crystal lattice of halide perovskites facilitates the coupled transport of ions and electrons, offering innovative concepts in semiconductor iontronic devices that surpass solar cell applications. However, a comprehensive understanding of the intricacies of coupled ionic and electronic transport at the microscale remains ambiguous, owing to the inhomogeneity in ploy-crystalline perovskite thin films. In this work, we employed one-dimensional (1D) single-crystalline CsPbBr3 nanowires (NWs) to investigate the electric field induced ionic transport. Upon poling by an external bias, the previously uniform NW exhibits highly anisotropic ionic transport, which is identified as the origin of the giant switchable photovoltaic effect by spatially resolved scanning photocurrent microscopy. The subsequent ultrafast scanning photoluminescence (PL) microscopy measurements demonstrate significant localization of photocarriers near one terminal of the device, which is attributed to the accumulation of halogen vacancies. In addition, thanks to the enhancement of the local electric field, the poled device shows a 10-fold increase of photoresponse speed. Our findings favor the scale-down of perovskite devices to the submicrometer scale, extending their applications in self-powered iontronic and optoelectronic devices.

Highly Anisotropic Polarization Induced by Electrical Poling in Single-Crystalline All-Inorganic Perovskite Nanoplates.

The coupled ionic and electronic transport in halide perovskites opens up new possibilities for semiconductor iontronic devices beyond solar cells. Nevertheless, the fundamental understanding of ionic behavior at the microscale remains vague, largely because of the inhomogeneity in polycrystalline thin films. Here, we show that the ion dynamics in single-crystalline perovskite nanoplates (NPs) are significantly different and that an external bias may induce highly anisotropic ionic transport in the NPs, thereby leading to a greatly enhanced local electric field. Using modified scanning photocurrent microscopy (SPCM), the origin of the photocurrent is pinpointed to the cathode region of the NP device, where subsequent energy dispersive spectroscopy (EDS) characterization confirms a large accumulation of halogen vacancies. In addition, the Kelvin probe force microscopy (KPFM) measurement demonstrates a strong built-in electric field within a submicron length near the cathode, which alters the local electronic structure for efficient photo carrier separation. Such field-induced ionic behavior deepens the understanding of ion dynamics in perovskites and promotes scale-down of perovskite micro- and nanoiontronic and ion-optoelectronic devices.

Topology-sensitive weighting model for myocardial segmentation.

Accurate myocardial segmentation is crucial for the diagnosis of various heart diseases. However, segmentation results often suffer from topology structural errors, such as broken connections and holes, especially in cases of poor image quality. These errors are unacceptable in clinical diagnosis. We proposed a Topology-Sensitive Weight (TSW) model to keep both pixel-wise accuracy and topological correctness. Specifically, the Position Weighting Update (PWU) strategy with the Boundary-Sensitive Topology (BST) module can guide the model to focus on positions where topological features are sensitive to pixel values. The Myocardial Integrity Topology (MIT) module can serve as a guide for maintaining myocardial integrity. We evaluate the TSW model on the CAMUS dataset and a private echocardiography myocardial segmentation dataset. The qualitative and quantitative experimental results show that the TSW model significantly enhances topological accuracy while maintaining pixel-wise precision.

Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers.

Background: Angiogenesis is crucial in diabetic wound healing and is often impaired in diabetic foot ulcers (DFUs). Human dermal microvascular endothelial cells (HDMECs) are vital components in dermal angiogenesis; however, their functional and transcriptomic characteristics in DFU patients are not well understood. This study aimed to comprehensively analyse HDMECs from DFU patients and healthy controls and find the potential regulator of angiogenesis in DFUs. Methods: HDMECs were isolated from skin specimens of DFU patients and healthy controls via magnetic-activated cell sorting. The proliferation, migration and tube-formation abilities of the cells were then compared between the experimental groups. Both bulk RNA sequencing (bulk-seq) and single-cell RNA-seq (scRNA-seq) were used to identify RAB17 as a potential marker of angiogenesis, which was further confirmed via weighted gene co-expression network analysis (WGCNA) and least absolute shrink and selection operator (LASSO) regression. The role of RAB17 in angiogenesis was examined through in vitro and in vivo experiments. Results: The isolated HDMECs displayed typical markers of endothelial cells. HDMECs isolated from DFU patients showed considerably impaired tube formation, rather than proliferation or migration, compared to those from healthy controls. Gene set enrichment analysis (GSEA), fGSEA, and gene set variation analysis (GSVA) of bulk-seq and scRNA-seq indicated that angiogenesis was downregulated in DFU-HDMECs. LASSO regression identified two genes, RAB17 and CD200, as characteristic of DFU-HDMECs; additionally, the expression of RAB17 was found to be significantly reduced in DFU-HDMECs compared to that in the HDMECs of healthy controls. Overexpression of RAB17 was found to enhance angiogenesis, the expression of hypoxia inducible factor-1α and vascular endothelial growth factor A, and diabetic wound healing, partially through the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling pathway. Conclusions: Our findings suggest that the impaired angiogenic capacity in DFUs may be related to the dysregulated expression of RAB17 in HDMECs. The identification of RAB17 as a potential molecular target provides a potential avenue for the treatment of impaired angiogenesis in DFUs.

Benzoquinone and furopyridinone derivatives from the marine-derived fungus Talaromyces sp. MCCC 3A01752.

Two new compounds, compounds 1 and 2, were obtained from the culture of a marine-derived fungus Talaromyces sp. MCCC 3A01752, together with 13 known compounds (3-15). Their structures were elucidated based on detailed analysis of NMR, HRESIMS, ECD spectra and OR value. Compound 1 exhibited antibacterial potential against Staphylococcus aureus with a MIC value of 100 µM and cytotoxic activity against gastric cancer cell line MKN1 with a IC50 value of 78.0 µM.

Infectious shock after liposuction.

BACKGROUND: Liposuction has become one of the most popular cosmetic surgeries in China. However, few studies have discussed infectious shock caused by C. perfringens as one of the causes of death after liposuction. CASE PRESENTATION: A 24-year-old woman was brought to the emergency department (ED) of Guangzhou Chinese Overseas Hospital for treatment. The patient had undergone liposuction in her bilateral lower limbs two days prior. At the ED, the patient was unconscious, and had bilateral equal-sized (diameter, 6 mm) round pupils, no light reflex, a blood pressure (BP) of 71/33 mmHg, a heart rate of 133 bpm, and an SpO2 of 70%. She had bilateral limb swelling, extensive ecchymoses in her lower abdomen and bilateral thighs, local crepitus, blisters, weak pulses on her femoral artery and dorsalis pedis, high skin tension, and hemoglobin of 32 g/L. The patient was diagnosed with Clostridium perfringens infection, and she underwent debridement surgery and supportive treatment. But the patient's BP could not improve. At 8:28 pm on the day of admission, the patient was declared clinically dead after the electrocardiograph showed a horizontal line and spontaneous respiration ceased. CONCLUSIONS: Failure to meet surgical disinfection and environmental standards may be the cause of infection of C. perfringens through wounds. Therefore, it is necessary to strengthen the environmental disinfection of the operating room, and standardize the sterile conditions of the operation staff and patients before and during operation. Liposuction surgery necrotizing fasciitis is a rare but fatal complications, especially if diagnosis delay, therefore it is critical for early diagnosis and treatment of gas gangrene.

Carbon Arc Lamp Therapy Enhances the Repair Potential of Chronic Soft Tissue Injury in Rats Compared with the Ability of Photobiomodulation Therapy.

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.

Elevated CO2 and soil mercury stress affect photosynthetic characteristics and mercury accumulation of rice.

This is a novel study about responses of leaf photosynthetic traits and plant mercury (Hg) accumulation of rice grown in Hg polluted soils to elevated CO2 (ECO2). The aim of this study was to provide basic information on the acclimation capacity of photosynthesis and Hg accumulation in rice grown in Hg polluted soil under ECO2 at day, night, and full day. For this purpose, we analyzed leaf photosynthetic traits of rice at flowering and grain filling. In addition, chlorophyll content, soluble sugar and Malondialdehyde (MDA) of rice leaves were measured at flowering. Seed yield, ear number, grain number per ear, 1000-grain weight, total mercury (THg) and methylmercury (MeHg) contents were determined after harvest. Our results showed that Hg polluted soil and ECO2 had no significant effect on leaf chlorophyll content and leaf mass per area (LMA) in rice. The contents of soluble sugar and MDA in leaves increased significantly under ECO2. Mercury polluted soil treatment significantly reduced the light saturated CO2 assimilation rate (Asat) of rice leaves only at flowering, but not at grain filling. Night ECO2 greatly improved rice leaf water use efficiency (WUE). ECO2 greatly increased seed yield and ear number. In addition, ECO2 did not affect THg accumulation in rice organs, but ECO2 and Hg treatment had a significant interaction on MeHg in seeds, husks and roots.

Decellularized adipose tissue: A key factor in promoting fat regeneration by recruiting and inducing mesenchymal stem cells.

BACKGROUND: Decellularized adipose tissue (DAT) has attracted much attention due to its wide range of sources and adipose regeneration capacity. However, the lipogenic efficiency of DAT is still controversial due to its unclear mechanism. To this point, it is crucial to clarify the mechanism of DAT in promoting adipose regeneration Objective: This study aims to explore the mechanism of DAT promoting adipose regeneration and survival mechanism of DAT transplantation in vivo. METHODS: DAT preparation by repeated freeze-thaw, enzymatic digestion, and isopropanol degreasing. Histology, DAPI, immunohistochemistry, immunofluorescence and scanning electron microscopy confirmed the efficacy and reproducibility of these approaches. BM-MSCs, ADSCs and UCMSCs were cocultured with DAT for 14 days and then stained with oil red O. Adipogenic genes of three MSCs were detected by RT-PCR. DAT and adipose tissue were transplanted subcutaneously into the back of nude mice to observe medium and long-term morphological changes, vascularization, and lipid-forming efficiency. Mass spectrometry (MS)-based proteomic to analyze the adipogenic protein contents of DAT and adipose tissue. RESULTS: The DAT without any cellular components but with an abundance of collagen; neither DNA nor lipids were detected. Seeding experiments with MSCs indicated that the DAT provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARγ. Within four months after transplantation, HE morphology of DAT was identical to adipose cells. Immunofluorescence markers CD31 and perilipin were increased in DAT, while the retention rate gradually decreased over time, eventually accounting for 33.7% of the original volume. MS-based proteomic analyses identified 1013 types of proteins in adipose tissue and 29 proteins in the DAT. Analyses of GO and KEGG databases suggested that DAT contained a variety of proteins involved in fat metabolism. CONCLUSIONS: DAT can interact with different types of MSCs and ultimately achieve adipose regeneration. The presence of multiple adipogenic proteins in DAT make it play a vital role in adipose regeneration. DAT is expected to be an ideal bio-derived scaffold for adipose tissue engineering.

Concentrated nanofat: a modified fat extraction promotes hair growth in mice via the stem cells and extracellular matrix components interaction.

BACKGROUND: Fat graft transplantation seems a promising cell therapy for hair loss. However, impurities in lipoaspirate weaken the treatment effect. Here, we developed the lipoaspirate extraction method then investigate the effect and mechanism on hair growth-promoting in a mouse model. METHODS: Fat graft was prepared into concentrated nanofat (CNF), decellularized CNF (DCNF), and adipose-derived stem cells (ADSCs). They were injected subcutaneously in the back of depilated mice to test the hair promoting effect. Conditioned media (CM) from the adipose extracts were applied to dermal papilla cells (DPCs) to evaluate the cell viability and the anagen related signal. RESULTS: CNF and a high dose of ADSCs promoted hair growth and induced telogen-to-anagen transition in depilated mice. DCNF and a low dose of ADSCs did not show such effect; however, hair growth was promoted when they were used in combination. In vitro study showed the CNF-CM treated DPCs exhibited increased proliferation, migration, cell cycle progression, and elevated Wnt/ß-catenin pathway protein levels compared with the other treatment groups. CONCLUSIONS: CNF has a better effect than ADSCs in hair promotion via activating the DPCs and anagen induction. In this nature complex of stem cells (SCs) and extracellular matrix (ECM), ECM serves a significant supplementary role and amplifies the power of ADSCs. These results supply a theoretical basis on the clinical application of CNF to treat hair loss.

Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor.

Cartilage tissue engineering is believed to provide effective cartilage repair post-injuries or diseases. Biomedical materials play a key role in achieving successful culture and fabrication of cartilage. The physical properties of a chitosan/gelatin hybrid hydrogel scaffold make it an ideal cartilage biomimetic material. In this study, a chitosan/gelatin hybrid hydrogel was chosen to fabricate a tissue-engineered cartilage in vitro by inoculating human adipose-derived stem cells (ADSCs) at both dynamic and traditional static culture conditions. A bioreactor that provides a dynamic culture condition has received greater applications in tissue engineering due to its optimal mass transfer efficiency and its ability to simulate an equivalent physical environment compared to human body. In this study, prior to cell-scaffold fabrication experiment, mathematical simulations were confirmed with a mass transfer of glucose and TGF-ß2 both in rotating wall vessel bioreactor (RWVB) and static culture conditions in early stage of culture via computational fluid dynamic (CFD) method. To further investigate the feasibility of the mass transfer efficiency of the bioreactor, this RWVB was adopted to fabricate three-dimensional cell-hydrogel cartilage constructs in a dynamic environment. The results showed that the mass transfer efficiency of RWVB was faster in achieving a final equilibrium compared to culture in static culture conditions. ADSCs culturing in RWVB expanded three times more compared to that in static condition over 10 days. Induced cell cultivation in a dynamic RWVB showed extensive expression of extracellular matrix, while the cell distribution was found much more uniformly distributing with full infiltration of extracellular matrix inside the porous scaffold. The increased mass transfer efficiency of glucose and TGF-ß2 from RWVB promoted cellular proliferation and chondrogenic differentiation of ADSCs inside chitosan/gelatin hybrid hydrogel scaffolds. The improved mass transfer also accelerated a dynamic fabrication of cell-hydrogel constructs, providing an alternative method in tissue engineering cartilage.

In vitro and in vivo study of hydralazine, a potential anti-angiogenic agent.

Hydralazine (HYD), an old routine clinical anti-hypertension drug, is rarely used in clinic nowadays. Since the strategy of repositioning old drugs was put forward, HYD has been reported to possess various biological activities, including antitumor efficacy and reducing intra-tumor microvessel. Here, we investigated that whether HYD had the ability of anti-angiogeneis and its underlying mechanism. Cells proliferation, wound-healing, Transwell migration and invasion, tube formation and rat aortic ring assays in vitro and chicken chorioallantoic membrane (CAM) model in vivo were designed to investigated HYD's anti-angiogenic effect. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed by enzyme-linked immune sorbent assay (ELISA). Hepatocellular carcinoma (HCC) mice model was used to evaluate HYD's effect on tumor growth and microvessel density. Our results showed that HYD not only inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, wound-healing, Transwell migration and invasion and tube formation, but also suppressed the microvessel outgrowth of rat aortic ring in vitro and the neovascularzation of CAM in vivo. Furthermore, we demonstrated that HYD attenuated tumor angiogenesis and tumor growth. In the co-culture system of Transwell migration, the secretion of VEGF and bFGF was reduced by HYD respectively. In sum, our data indicate that HYD has the pharmacological effect of ant-angiogenesis by interference with VEGF and bFGF signaling pathways in endothelial cells. These findings suggest that HYD might be a promising angiogenesis inhibitor and a potential effective therapeutic agent for cancer therapy.