Pheochromocytoma-induced diffuse alveolar hemorrhage after cholecystectomy: A case report and literature review.

Diffuse alveolar hemorrhage (DAH) can be caused by various conditions, categorized as autoimmune and non-autoimmune. Immunofactor-mediated vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, and antiphospholipid antibody syndrome, are common autoimmune causes. Non-autoimmune factors include infectious or toxic exposures and neoplastic conditions. The diagnosis of DAH, resulting from excessive catecholamine release from an adrenal pheochromocytoma or extra-adrenal paraganglioma, can present diagnostic challenges and necessitate prompt treatment. In this report, we present a case of pheochromocytoma that manifested as an adrenal incidentaloma (diagnosed during the management of sudden-onset DAH after cholecystectomy). Case report: A 39-year-old female patient with adrenal incidentaloma developed DAH following a cholecystectomy procedure, presenting with sudden-onset hemoptysis and dyspnea. Administration of glucocorticoids, known to precipitate pheochromocytoma crisis (PCC), was required before the cause was determined. Intubation and mechanical ventilation were necessary due to persistent hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). The patient in this case experienced two epidoses of PCC while she was on mechanical ventilation. Subsequent work-up revealed a 26 × 25 mm left adrenal adenoma with hormonal confirmation of catecholamine hypersecretion. A laparoscopic adrenalectomy was done eight months later to excise the left adrenal gland. Subsequent examination of the tissue revealed pheochromocytoma, thereby validating the initial diagnosis. Conclusion: Adrenal incidentalomas may be pheochromocytomas (adrenal incidentalomas can manifest as pheochromocytomas), even without adrenergic symptoms. It is recommended that adrenal incidentalomas undergo evaluation for pheochromocytoma before undergoing invasive surgery or receiving corticosteroid treatment. When considering potential causes of DAH without further elucidation, including a pheochromocytoma or paraganglioma (PPGLs) in the differential diagnosis is important.

ASIC3-activated key enzymes of de novo lipid synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells.

Acidic microenvironments is a cancer progression driver, unclear core mechanism hinders the discovery of new diagnostic or therapeutic targets. ASIC3 is an extracellular proton sensor and acid-sensitive, but its role in acidic tumor microenvironment of colorectal cancer is not reported. Functional analysis data show that colorectal cancer cells respond to specific concentration of lactate to accelerate invasion and metastasis, and ASIC3 is the main actor in this process. Mechanism reveal de novo lipid synthesis is a regulatory process of ASIC3, down-regulated ASIC3 increases and interacts with ACC1 and SCD1, which are key enzymes in de novo lipid synthesis pathway, this interaction results in increased unsaturated fatty acids, which in turn induce EMT to promote metastasis, and overexpression of ASIC3 reduces acidic TME-enhanced colorectal cancer metastasis. Clinical samples of colorectal cancer also exhibit decreased ASIC3 expression, and low ASIC3 expression is associated with metastasis and stage of colorectal cancer. This study is the first to identify the role of the ASIC3-ACC1/SCD1 axis in acid-enhanced colorectal cancer metastasis. The expression pattern of ASIC3 in colorectal cancer differs significantly from that in other types of cancers, ASIC3 may serve as a novel and reliable marker for acidic microenvironmental in colorectal cancer, and potentially a therapeutic target.

Preparation and Properties of Multi-Responsive Liquid Crystalline Poly(urethane-acrylate)s and Its Composite Membranes.

In this work, a kind of side chain liquid crystalline poly(urethane-acrylate)s was synthesized by free polymerization based on self-made liquid crystalline monomers, and a series of liquid crystalline polyurethane/shape memory polyurethane composite membranes were prepared by electrospinning. The synthesized liquid crystalline poly(urethane-acrylate)s have excellent thermal stability. Due to the regular arrangement of azobenzene on the side chains, polymers can rapidly undergo a photoinduced transition from trans-isomerism to cis-isomerism in THF solution and restore reversible configurational changes under visible light. The composite membranes prepared by electrospinning can also undergo photoinduced deformation within 6 s, and the deformation slowly returns under visible light. Meanwhile, the composites have shape memory, and after deformation caused by stretching, the membranes can quickly recover their original shape under thermal stimulation. These results indicate that the composites have triple response performances of photoinduced deformation, photo-, and thermal recovery.

Discovery of Novel Oxathiapiprolin Derivatives as Potent Fungicide Candidates.

Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24 was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24 should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24 could be used as a lead compound for the discovery of new OSBP inhibitors.

Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles.

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.

High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway.

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating the intricacies of CRC cells initiation and progression within a high-glucose environment. METHODS: A battery of assays was employed to assess the proliferation and metastasis of CRC cells cultured under varying glucose concentrations. Optimal glucose levels conducive to cells' proliferation and migration were identified. Western blot analyses were conducted to evaluate alterations in apoptosis, autophagy, and EMT-related proteins in CRC cells under high-glucose conditions. The expression of PI3K/AKT/mTOR pathway-associated proteins was assessed using western blot. The effect of high glucose on xenograft growth was investigated in vivo by MC38 cells, and changes in inflammatory factors (IL-4, IL-13, TNF-α, IL-5, and IL-12) were measured via serum ELISA. RESULTS: Our experiments demonstrated that elevated glucose concentrations promoted both the proliferation and migration of CRC cells; the most favorable glucose dose is 20 mM. Western blot analyses revealed a decrease in apoptotic proteins, such as Bim, Bax, and caspase-3 with increasing glucose levels. Concurrently, the expression of EMT-related proteins, including N-cadherin, vimentin, ZEB1, and MMP9, increased. High-glucose cultured cells exhibited elevated levels of PI3K/AKT/mTOR pathway proteins. In the xenograft model, tumor cells stimulated by high glucose exhibited accelerated growth, larger tumor volumes, and heightened KI67 expression of immunohistochemistry. ELISA experiments revealed higher expression of IL-4 and IL-13 and lower expression of TNF-α and IL-5 in the serum of high-glucose-stimulated mice. CONCLUSION: The most favorable dose and time for tumor cells proliferation and migration is 20 mM, 48 h. High glucose fosters CRC cell proliferation and migration while suppressing autophagy through the activation of the PI3K/AKT/mTOR pathway.

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.

BACKGROUND: The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. METHODS: Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. RESULTS: We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. CONCLUSIONS: Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.

Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles: Sequential Embryo Transfer or Double-blastocyst Transfer?

OBJECTIVE: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes. METHODS: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes. RESULTS: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT. CONCLUSION: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

One-Step Syntheses of 3,4-Disubstituted Isochroman-1-ones by the Annulation of Benzoic Acids with Nitroalkenes.

The Rh(III)-catalyzed annulation of benzoic acids with nitroalkenes was disclosed to afford a wide range of 3,4-disubstituted isochroman-1-ones with excellent regioselectivity and high catalytic efficiency. Both aromatic and aliphatic nitroalkenes participated in this cyclization reaction successfully. The synthetic value of 3,4-disubstituted isochroman-1-ones was proven by a series of derivatizations. Furthermore, a reliable mechanism is outlined on the basis of experimental investigations and related precedents.

The Protective Effect of a Human Umbilical Cord Mesenchymal Stem Cell Supernatant on UVB-Induced Skin Photodamage.

The skin is constantly exposed to a range of environmental stressors, including ultraviolet (UV) radiation, which can cause damage to the skin. Repairing UV-damaged skin has been a major focus of research in recent years. The therapeutic potential of human umbilical cord mesenchymal stem cells (HUCMSCs) exhibits anti-photoaging properties. In this study, we developed a strategy for concentrating an HUCMSC supernatant, and examined the protective effects of CHS on UVB exposure in vitro and in vivo. Our results demonstrate that CHS repairs UVB exposure by promoting cell viability and migration and reducing senescent and apoptosis cells. We further found that the photoprotective effect of CHS is due to autophagy activation. Moreover, CHS reduces wrinkles and senescent cells, increases collagen expression, and improves immune function in UVB exposure-induced skin damage. In summary, our study provides a new approach for repairing cell damage, and suggests that CHS might be a potential candidate for preventing UVB-induced skin photodamage.