Pulmonary Tuberculosis Complicated by Thrombotic Thrombocytopenic Purpura: A Case Report and Literature Review.

Thrombotic thrombocytopenic purpura is a rare but life-threatening emergency. Tuberculosis can have hematologic complications. However, concurrent tuberculosis and thrombotic thrombocytopenic purpura are extremely rare. In this study, we report a 53-year-old man who was initially treated for pulmonary tuberculosis but later developed weakness and an altered mental status. Laboratory tests revealed evidence of thrombocytopenia, acute renal insufficiency, and microangiopathic hemolytic anemia. Brain imaging identified intracranial hemorrhage. Further testing revealed low ADAMTS13 activity (1.8%) and positive anti-ADAMTS13 antibody, confirming the diagnosis of thrombotic thrombocytopenic purpura. The patient had a full recovery after anti-tuberculosis treatment, plasma exchange, and supportive care. We present this rare case and review previous relevant studies to remind clinicians about the potential connections between tuberculosis and thrombotic thrombocytopenic purpura. In patients with signs of severe thrombocytopenia and microangiopathic hemolysis, necessary diagnostic tests should be performed to eliminate the possibility of thrombotic thrombocytopenic purpura occurring concurrently with tuberculosis.

Synthesis of 1,2,4-diazaphospholes via base-promoted cyclization reaction of hydrazonoyl chlorides and [Bu4N][P(SiCl3)2].

Aromatic 1,2,4-diazaphospholes featuring distinct hybrid-mode nitrogen atoms (N(λ3σ2), N(λ3σ3)) and low-valent phosphorus atoms (λ3σ2) exhibited the characteristic of serving as unique hybrid ligands. This study presented a one-pot reaction involving the base-promoted stepwise cyclization of hydrazonoyl chlorides and [Bu4N][P(SiCl3)2] to yield 1,2,4-diazaphospholes, providing an effective method for synthesizing such compounds.

Development and Validation of a Stromal-Immune Signature to Predict Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Taking Photoacoustic Force into Account in Liquid-Phase Peak Force Infrared Microscopy.

The microscopic structure of the material's solid-liquid interface significantly influences its physicochemical properties. Peak force infrared microscopy (PFIR) is a powerful technique for analyzing these interfaces at the nanoscale, revealing crucial structure-activity relationships. PFIR is recognized for its explicit photothermal signal generation mechanism but tends to overlook other photoinduced forces, which can disturb the obtained infrared spectra, thereby reducing spectral signal-to-noise ratio (SNR) and sensitivity. We have developed a multiphysics-coupled theoretical model to assess the magnitudes of various photoinduced forces in PFIR experiments and have found that the magnitude of the photoacoustic force is comparable to that of the photothermal expansion force in a liquid environment. Our calculations show that through simple modulation of the pulse waveform it is possible to effectively suppress the photoacoustic interference, thereby improving the SNR and sensitivity of PFIR. This work aims to alert researchers to the potential for strong photoacoustic interference in liquid-phase PFIR measurements and enhance the performance of PFIR by clarifying the photoinduced forces entangled in the signals.

[Research progress on effect evaluation and application status of acupoint drug delivery].

Acupoint drug delivery is a traditional external therapy of traditional Chinese medicine(TCM). Guided by the meridian and collateral theory in TCM, it applies medications to the skin at acupoints, exerting a dual therapeutic effect by stimulating the acupoints and the conduction of meridians. Acupoint drug delivery is widely used in clinical practice. Different from traditional oral admi-nistration and injection, it absorbs medications through the skin, effectively avoiding the first-pass effect of drugs and the toxic side effects caused by injection. Acupoint selection and transdermal drug absorption are pivotal factors affecting the efficacy of acupoint drug delivery. Recent research on acupoint drug delivery mainly focuses on the evaluation of clinical efficacy, yet the systematic investigations on acupoint selection and pharmacodynamic factors are scarce. This study reviews the mechanism, efficacy evaluation and application status of acupoint drug delivery. It integrates the theory of TCM with modern medicine to explore the mechanism of acupoint drug delivery, evaluate its clinical efficacy, and assess the transdermal penetration in vivo and in vitro. The application status of acupoint drug delivery is also summarized, including the selection of acupoints, application dosage form, application time and the absorption of acupoints. This review aims to offer insights and references for the research, development and clinical application of acupoint drug delivery products.

Natural Products from Herbal Medicine Self-Assemble into Advanced Bioactive Materials.

Novel biomaterials are becoming more crucial in treating human diseases. However, many materials require complex artificial modifications and synthesis, leading to potential difficulties in preparation, side effects, and clinical translation. Recently, significant progress has been achieved in terms of direct self-assembly of natural products from herbal medicine (NPHM), an important source for novel medications, resulting in a wide range of bioactive supramolecular materials including gels, and nanoparticles. The NPHM-based supramolecular bioactive materials are produced from renewable resources, are simple to prepare, and have demonstrated multi-functionality including slow-release, smart-responsive release, and especially possess powerful biological effects to treat various diseases. In this review, NPHM-based supramolecular bioactive materials have been revealed as an emerging, revolutionary, and promising strategy. The development, advantages, and limitations of NPHM, as well as the advantageous position of NPHM-based materials, are first reviewed. Subsequently, a systematic and comprehensive analysis of the self-assembly strategies specific to seven major classes of NPHM is highlighted. Insights into the influence of NPHM structural features on the formation of supramolecular materials are also provided. Finally, the drivers and preparations are summarized, emphasizing the biomedical applications, future scientific challenges, and opportunities, with the hope of igniting inspiration for future research and applications.

Mesenchymal Stem Cell Membrane-Camouflaged Liposomes for Biomimetic Delivery of Cyclosporine A for Hepatic Ischemia-Reperfusion Injury Prevention.

Hepatic ischemia-reperfusion injury (HIRI) is a prevalent issue during liver resection and transplantation, with currently no cure or FDA-approved therapy. A promising drug, Cyclosporin A (CsA), ameliorates HIRI by maintaining mitochondrial homeostasis but has systemic side effects due to its low bioavailability and high dosage requirements. This study introduces a biomimetic CsA delivery system that directly targets hepatic lesions using mesenchymal stem cell (MSC) membrane-camouflaged liposomes. These hybrid nanovesicles (NVs), leveraging MSC-derived proteins, demonstrate efficient inflammatory chemotaxis, transendothelial migration, and drug-loading capacity. In a HIRI mouse model, the biomimetic NVs accumulated at liver injury sites entered hepatocytes, and significantly reduced liver damage and restore function using only one-tenth of the CsA dose typically required. Proteomic analysis verifies the protection mechanism, which includes reactive oxygen species inhibition, preservation of mitochondrial integrity, and reduced cellular apoptosis, suggesting potential for this biomimetic strategy in HIRI intervention.

Inductive State-Relabeling Adversarial Active Learning with Heuristic Clique Rescaling.

Active learning (AL) is to design label-efficient algorithms by labeling the most representative samples. It reduces annotation cost and attracts increasing attention from the community. However, previous AL methods suffer from the inadequacy of annotations and unreliable uncertainty estimation. Moreover, we find that they ignore the intra-diversity of selected samples, which leads to sampling redundancy. In view of these challenges, we propose an inductive state-relabeling adversarial AL model (ISRA) that consists of a unified representation generator, an inductive state-relabeling discriminator, and a heuristic clique rescaling module. The generator introduces contrastive learning to leverage unlabeled samples for self-supervised training, where the mutual information is utilized to improve the representation quality for AL selection. Then, we design an inductive uncertainty indicator to learn the state score from labeled data and relabel unlabeled data with different importance for better discrimination of instructive samples. To solve the problem of sampling redundancy, the heuristic clique rescaling module measures the intra-diversity of candidate samples and recurrently rescales them to select the most informative samples. The experiments conducted on eight datasets and two imbalanced scenarios show that our model outperforms the previous state-of-the-art AL methods. As an extension on the cross-modal AL task, we apply ISRA to the image captioning and it also achieves superior performance.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

[Corrigendum] Macrophage­secreted IL­8 induces epithelial­mesen-chymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a possible error had been identified in the selection of images in Figs. 1 and/or 7. After having consulted their original data, the authors realized that an erroneous image appeared on p. 593, in Fig. 7F [the 'Hep­G2 / IL­8 (5 ng/ml)' data panel], where part of this figure panel was overlapping with an image on p. 589 in Fig. 1C (the 'Hep­G2 Co­cultured' data panel). After a thorough review and verification of the data by all the authors, they have confirmed that the original data presented in the paper were accurate, and the error was solely due to the selection of an incorrect image during figure arrangement. The authors confirm that this mistake in image selection did not affect the overall conclusions reported in the article. A corrected version of Fig. 7, including the correct data for the 'Hep­G2 / IL­8 (5 ng/ml)' panel in Fig. 7F, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this Corrigendum. All the authors agree to the publication of this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 587­596, 2015; DOI: 10.3892/ijo.2014.2761].

Spatial accumulation of lignin monomers and cellulose underlying stalk strength in maize.

Lodging largely affects yield, quality and mechanical harvesting of maize. Stalk strength is one of the major factors that affect maize lodging. Although plant cell wall components including lignin and cellulose were known to be associated with stalk strength and lodging resistance, spatial accumulation of specific lignin monomers and cellulose in different tissues and their association with stalk strength in maize was not clearly understood. In this study, we found that both G and S lignin monomers accumulate highest in root, stem rind and leaf vein. Consistently, most lignin biosynthetic genes were expressed higher in root and stem than in other tissues. However, cellulose appears to be lowest in root. There are only mild changes of G lignin and cellulose in different internodes. Instead, we noticed a dramatic decrease of S-lignin accumulation and lignin biosynthetic gene expression in 2nd to 4th internodes wherein stem breakage usually occurs, thereby revealing a few candidate lignin biosynthetic genes associated with stalk strength. Moreover, stalk strength is positively correlated with G, S lignin, and cellulose, but negatively correlated with S/G ratio based on data of maize lines with high or low stalk strength. Loss-of-function of a caffeic acid o-methyltransferase (COMT), which is involved in S lignin biosynthesis, in the maize bm3 mutant, leads to lower stalk strength. Our data collectively suggest that stalk strength is determined by tissue-specific accumulation of lignin monomers and cellulose, and manipulation of the cell wall components by genetic engineering is vital to improve maize stalk strength and lodging resistance.

An analytical method to estimate the accuracy representation index of circular and elliptical disc models for rectangular fractures with application to seepage analysis.

Constructing a suitable discrete fracture network (DFN) to represent rock fractures proves vital for tackling engineering projects involving rock masses. Among the commonly used models for constructing DFN, the circular disc model (CDM) and elliptical disc model (EDM) stand out. The selection between these models has been facilitated by the introduction of the Accuracy Representation Index (ARI), which quantitatively assesses their suitability. The existing methods for calculating ARI based on Monte Carlo simulations are time-consuming. In order to quickly estimate the ARI for CDM and EDM concerning any length-width ratio (k r ) of rectangular fracture, the paper derives analytical formulas based on the geometric relationships between circles and ellipses with rectangles. These formulas show that: (a) for the CDM, ARI is only related to k r , and its value decreases as k r increases; (b) for the EDM, ARI is dependent on the relationship between k r and the long-short axis length ratio (k e ) of the ellipse, and it has been theoretically proven that ARI reaches its maximum value of 0.91 when k r is equal to k e . Moreover, we apply ARI to the study of rock mass seepage characteristics, and the results show that ARI could reflect the error rate of permeability of the CDM and EDM for rock masses with rectangular fractures.

Event-based Optical Flow via Transforming into Motion-dependent View.

Event cameras respond to temporal dynamics, helping to resolve ambiguities in spatio-temporal changes for optical flow estimation. However, the unique spatio-temporal event distribution challenges the feature extraction, and the direct construction of motion representation through the orthogonal view is less than ideal due to the entanglement of appearance and motion. This paper proposes to transform the orthogonal view into a motion-dependent one for enhancing event-based motion representation and presents a Motion View-based Network (MV-Net) for practical optical flow estimation. Specifically, this motion-dependent view transformation is achieved through the Event View Transformation Module, which captures the relationship between the steepest temporal changes and motion direction, incorporating these temporal cues into the view transformation process for feature gathering. This module includes two phases: extracting the temporal evolution clues by central difference operation in the extraction phase and capturing the motion pattern by evolution-guided deformable convolution in the perception phase. Besides, the MV-Net constructs an eccentric downsampling process to avoid response weakening from the sparsity of events in the downsampling stage. The whole network is trained end-to-end in a self-supervised manner, and the evaluations conducted on four challenging datasets reveal the superior performance of the proposed model compared to state-of-the-art (SOTA) methods.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Potentiating dual-directional immunometabolic regulation with nanomedicine to enhance anti-tumor immunotherapy following incomplete photothermal ablation.

Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Synthesis of Azabicyclo[3.1.1]heptenes Enabled by Catalyst-Controlled Annulations of Bicyclo[1.1.0]butanes with Vinyl Azides.

Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept of "escape from flatland". However, adopting this concept into the exploration of bioisosteres of pyridines remains elusive due to the challenge of incorporating a N atom into such bridged bicyclic structures. Herein, we report practical routes for the divergent synthesis of 2- and 3-azabicyclo[3.1.1]heptenes (aza-BCHepes) as potential bioisosteres of pyridines from the readily accessible vinyl azides and bicyclo[1.1.0]butanes (BCBs) via two distinct catalytic annulations. The reactivity of vinyl azides tailored with BCBs is the key to achieving divergent transformations. TiIII-catalyzed single-electron reductive generation of C-radicals from BCBs allows a concise (3 + 3) annulation with vinyl azides, affording novel 2-aza-BCHepe scaffolds. In contrast, scandium catalysis enables an efficient dipolar (3 + 2) annulation with vinyl azides to generate 2-azidobicyclo[2.1.1]hexanes, which subsequently undergo a chemoselective rearrangement to construct 3-aza-BCHepes. Both approaches efficiently deliver unique azabicyclo[3.1.1]heptene scaffolds with a high functional group tolerance. The synthetic utility has been further demonstrated by scale-up reactions and diverse postcatalytic transformations, providing valuable azabicyclics including 2- and 3-azabicyclo[3.1.1]heptanes and rigid bicyclic amino esters. In addition, the related sp2-hybridized nitrogen atom and the similar geometric property between pyridines and corresponding aza-BCHepes indicate that they are promising bioisosteres of pyridines.

Rapid in situ formation of κ-carrageenan-carboxymethyl chitosan-kaolin clay hydrogel films enriched with arbutin for enhanced preservation of cherry tomatoes.

Food waste resulting from perishable fruits and vegetables, coupled with the utilization of non-renewable petroleum-based packaging materials, presents pressing challenges demanding resolution. This study addresses these critical issues through the innovative development of a biodegradable functional plastic wrap. Specifically, the proposed solution involves the creation of a κ-carrageenan/carboxymethyl chitosan/arbutin/kaolin clay composite film. This film, capable of rapid in-situ formation on the surfaces of perishable fruits, adeptly conforms to their distinct shapes. The incorporation of kaolin clay in the composite film plays a pivotal role in mitigating water vapor and oxygen permeability, concurrently bolstering water resistance. Accordingly, tensile strength of the composite film experiences a remarkable enhancement, escalating from 20.60 MPa to 34.71 MPa with the incorporation of kaolin clay. The composite film proves its efficacy by preserving cherry tomatoes for an extended period of 9 days at 28 °C through the deliberate delay of fruit ripening, respiration, dehydration and microbial invasion. Crucially, the economic viability of the raw materials utilized in the film, coupled with the expeditious and straightforward preparation method, underscores the practicality of this innovative approach. This study thus introduces an easy and sustainable method for preserving perishable fruits, offering a cost-effective and efficient alternative to petroleum-based packaging materials.

[Ectopic pituitary tumor of sphenoid sinus: a case report].

Ectopic pituitary adenoma is rare in clinical practice. This article reports a case of ectopic pituitary adenoma of sphenoid sinus, and summarizes the clinical characteristics, diagnosis and management. A 54-year-old female patient complaining with occasional head distension without dizziness and headache for more than 1 month was admitted due to sinus mass on conventional physical examination. Imaging examination revealed a mass in the occipital slope and bilateral sphenoid sinus. The patient underwent endoscopic resection of the mass under general anesthesia. Postoperative histopathological examination showed "pituitary neuroendocrine tumor". Postoperative recovery was good and no complications occurred. She was followed up for 2 months without relapse.

Event-based asynchronous HDR imaging by temporal incident light modulation.

Dynamic range (DR) is a pivotal characteristic of imaging systems. Current frame-based cameras struggle to achieve high dynamic range imaging due to the conflict between globally uniform exposure and spatially variant scene illumination. In this paper, we propose AsynHDR, a pixel-asynchronous HDR imaging system, based on key insights into the challenges in HDR imaging and the unique event-generating mechanism of dynamic vision sensors (DVS). Our proposed AsynHDR system integrates the DVS with a set of LCD panels. The LCD panels modulate the irradiance incident upon the DVS by altering their transparency, thereby triggering the pixel-independent event streams. The HDR image is subsequently decoded from the event streams through our temporal-weighted algorithm. Experiments under the standard test platform and several challenging scenes have verified the feasibility of the system in HDR imaging tasks.