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A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. , transforming growth factor-β1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts-macrophages communication may provide a novel therapeutic target for kidney fibrosis.

Background End-expiratory lung volume (EELV) has been observed to decrease in acute respiratory distress syndrome (ARDS). Yet, research investigating EELV in patients with COVID-19 associated ARDS (CARDS) remains limited. It is unclear whether EELV could serve as a potential metric for monitoring disease progression and identifying patients with ARDS at increased risk of adverse outcomes. Study design and methods This retrospective study included mechanically ventilated patients diagnosed with CARDS during the initial phase of epidemic control in Shanghai. EELV was measured using the nitrogen washout-washin technique within 48 h post-intubation, followed by regular assessments every 3–4 days. Chest CT scans, performed within a 24-hour window around each EELV measurement, were analyzed using AI software. Differences in patient demographics, clinical data, respiratory mechanics, EELV, and chest CT findings were assessed using linear mixed models (LMM). Results Out of the 38 patients enrolled, 26.3% survived until discharge from the ICU. In the survivor group, EELV, EELV/predicted body weight (EELV/PBW) and EELV/predicted functional residual capacity (EELV/preFRC) were significantly higher than those in the non-survivor group (survivor group vs. non-survivor group: EELV: 1455 vs. 1162 ml, P  = 0.049; EELV/PBW: 24.1 vs. 18.5 ml/kg, P  = 0.011; EELV/preFRC: 0.45 vs. 0.34, P  = 0.005). Follow-up assessments showed a sustained elevation of EELV/PBW and EELV/preFRC among the survivors. Additionally, EELV exhibited a positive correlation with total lung volume and residual lung volume, while demonstrating a negative correlation with lesion volume determined through chest CT scans analyzed using AI software. Conclusion EELV is a useful indicator for assessing disease severity and monitoring the prognosis of patients with CARDS.

The nitrogen-centered radical has been drawing increasing attention among researchers. Radical polarity is one of the key factors in studying nitrogen-centered radicals’ reactivity, and the functional groups attached to the nitrogen atom are of vital importance. Among different types of nitrogen-centered radicals, aminium radical and metal aminium radical are electrophilic due to the positive charge on the intermediate. The sulfonamide radical, amidyl radical, and cyanide amine radical are also electrophilic since the nitrogen is adjacent to electron electron-withdrawing group. The neutral amino radical, iminyl radical, masked nitrogen radical are nucleophilic because of the electron-donating groups. After classifying the nitrogen-centered radical, the generation and reactivity of these radicals are discussed in detail.One of the thesis projects is the spiro cyclic aminal photocatalytic ring-opening and monofunctionalization via distonic radical cation. The existing aminium radical studies mainly focus on the [3+2] annulation reactions, and the only exceptional example is the photocatalytic ring-opening and difunctionalization study with TMSCN from our group’s unpublished result. TMSCN helps to stabilize the aminium side of the radical cation to push the reaction forward. Inspired by the rearrangement reactivity of the cyclic aminal studies, we propose that the aminal can also help to stabilize the aminium side of the photocatalytic-generated distonic radical cation. The aminal photocatalytic ring-opening and monofunctionalization works well with the radical acceptor, many trifluoromethyl styrenes, and some variations on the aminal ring and cyclobutanone can also be achieved.The other project refers to photocatalytic ring-opening and monofunctionalization of the spiro hydro-benzoxazine featured with the N, O-acetal structure. Although designed to stabilize the distonic radical cation using the N, O-acetal, the reaction seems to go through the PCET pathway.In this case, the nickel-catalyzed C(sp2)-C(sp3) cross-coupling is tested to figure out whether it can fit in the PCET nitrogen neutral radical ring-opening system. The study gives another possible reactivity other than alkene addition, which is well-explored in the existing cyclic alkyl amine ring-opening studies. The optimization of the reaction is done, and further scope extension reveals more effect in the future study.

Far-from-equilibrium (FFE) conditions give rise to many unusual phenomena in nature. In contrast, synthetic shape-shifting materials typically rely on monotonic evolution between equilibrium states, limiting inherently the richness of the shape-shifting behaviors. Here we report an unanticipated shape-shifting behavior for a hydrogel that can be programmed to operate FFE-like behavior. During its temperature triggered shape-shifting event, the programmed stress induces uneven water diffusion, which pushes the hydrogel off the equilibrium based natural pathway. The resulting geometric change enhances the diffusion contrast in return, creating a self-amplifying sequence that drives the system into an FFE condition. Consequently, the hydrogel exhibits counterintuitive two opposite shape-shifting events under one single stimulation, at a speed accelerated by more than one order magnitude. Our discovery points to a future direction in creating FFE conditions to access otherwise unattainable shape-shifting behaviors, with potential implications for many engineering applications including soft robotics and medical devices. Synthetic shape-shifting materials typically rely on monotonic evolution between equilibrium states, limiting the shape-shifting behaviours. Here the authors report an unanticipated shape-shifting behaviour for a hydrogel that can be programmed to operate via a far-from-equilibrium mechanism.

Background Oncolytic virus has emerged as a promising candidate against tumors by infecting and killing cancer cells. In addition to poor prognosis of patients with glioma, the exact mechanisms driving the oncolytic virus therapy in glioma remain poorly understood. Methods We employed Enterovirus A71 (EV-A71)-based dataset (GSE136330), vesicular stomatitis virus (VSV)-M51-based dataset (GSE166914) and TCGA-glioma cohort to identify potential candidate gene after oncolytic virus infection. Then we investigated the correlation between glycogenin-2 (GYG2) and crucial outcomes such as clinical features, overall survival, tumor microenvironment. GO enrichment and GSEA analysis were performed to identify GYG2-coexpressed genes and potential regulatory pathways in glioma. The expression level of GYG2 in glioma tissues and cells was evaluated by qRT-PCR. Loss- and gain-of-function and rescue studies were used to explore the functional effect of GYG2 on glioma cell growth and apoptosis in VSV-M51-infected cells. Results Bioinformatics analysis show that GYG2 is downregulated after VSV-M51 or EV-A71 infection in glioma T98 cells. High expression of GYG2 in glioma is associated with high WHO grade and poor prognosis. In addition, GYG2 expression is linked with immune cell infiltration and immune microenvironment in glioma. GYG2 and its co-expressed protein are involved in regulating integrin 1 pathway and aurora B pathway in glioma. Downregulating GYG2 inhibits glioma cell growth and facilitates tumor cell apoptosis. Importantly, VSV-M51 infection promotes glioma cell apoptosis by downregulating GYG2. Conclusions Overall, this study advances our knowledge on the mechanisms of oncolytic virus infection and highlights a novel anti-apoptotic effect of GYG2 in glioma, further supporting it as an oncolytic virus target for therapy.

A robust Folin–Ciocalteu method, coupled with an optimized ultrasonic-assisted extraction, was established for accurate quantification of total polyphenols in high-oil grape seed matrices, where lipid interference and low extraction efficiency have been persistent challenges. Samples were first defatted with n-hexane to eliminate lipid interference. Key colorimetric parameters—Folin–Ciocalteu reagent volume, Na2CO3 concentration, reaction temperature, and time—were systematically optimized and validated for linearity, precision, and recovery. Subsequently, using defatted grape seed powder as the raw material, a four-factor, three-level Box–Behnken design combined with response surface methodology was employed to optimize the four extraction parameters: solid-to-liquid ratio, ethanol concentration, extraction temperature, and extraction time. The optimal conditions were 0.5 mL of Folin–Ciocalteu reagent, 20% Na2CO3, and reaction at 30 °C for 2.0 h, yielding a linear calibration curve (R2 = 0.9991) with satisfactory methodological validation. Optimal extraction (52% ethanol, 1:50 w/v, 68 °C, 21 min) achieved a total polyphenol content of 2.93 × 104 mg·kg−1, closely matching the predicted value (relative error = 0.34%). Analysis of seven grape seed varieties from the Hebei Province revealed significant content variation (p < 0.05), ranging from 3.24 to 7.47 × 104 mg·kg−1, with Rose grape seeds exhibiting the highest level. The developed method effectively overcame matrix interference from high oil content, offering a reliable, efficient tool for screening high-polyphenol grape seed varieties and supporting the development of value-added functional products.

Background and Aims Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. Methods Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. Results Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I–II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. Conclusion Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. Chinese Clinical Trial Registry Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

Liver diseases, particularly chronic conditions leading to cirrhosis and hepatocellular carcinoma, represent a major global health burden with high mortality rates, necessitating innovative diagnostic and therapeutic approaches. Ultrasound-targeted microbubble destruction (UTMD) technology has emerged as a promising theranostic platform, combining enhanced contrast imaging with targeted drug/gene delivery capabilities. When activated by ultrasound, these microbubbles exhibit unique biophysical behaviors that significantly improve drug penetration, tissue perfusion, and site-specific delivery. This review comprehensively examines recent advancements in UTMD-based strategies for liver disease management, including microbubble design and imaging-targeted functionalization, and mechanisms of ultrasound-enhanced drug delivery, especially emerging theranostic applications. We further discuss the underlying biophysical principles governing microbubble-ultrasound interactions and their translational potential, providing insights for developing next-generation precision medicine approaches for hepatic disorders.

This paper presents a compact switching model for enhancement-mode p-GaN HEMTs targeting high-speed driver circuit applications. The model is developed based on the Advanced SPICE Model (ASM) framework with a revised description of p-GaN-related inter-terminal capacitances. The proposed model accurately reproduces the transfer characteristics, output characteristics, and capacitance–voltage characteristics, with fitting errors below 5 %. To validate the model at the circuit level, all-GaN logic circuits and a high-speed driver circuit are designed and verified through simulation and experimental measurements. The results demonstrate that the model can accurately predict switching transient behavior under practical operating conditions, making it suitable for all-GaN driver circuit simulation and engineering design.

The Arctic has long been governed through a framework of cooperation, environmental stewardship, and diplomatic restraint—often conceptualized as Arctic exceptionalism. However, escalating geopolitical tensions and accelerating climate change increasingly challenge this governance paradigm. This study examines the Northern Sea Route (NSR) as a critical test case for assessing whether Arctic exceptionalism persists, erodes, or transforms under emerging global pressures. We develop an integrated analytical framework to evaluate the NSR’s strategic value (SV) across three interrelated dimensions: economic competitiveness, geopolitical reliability, and cooperation potential. Using panel regressions, we show that climate-induced sea-ice retreat and port efficiency enhance the NSR’s economic attractiveness, while rising geopolitical risks undermine navigational reliability—except during periods when disruptions to alternative routes elevate the NSR’s relative importance. A game-theoretic model further demonstrates that cooperative participation along the NSR is sustainable only under balanced surplus-sharing arrangements, whereas excessive rent extraction destabilizes collaboration. Scenario projections to 2030 indicate that coordinated governance and joint infrastructure investment can partially preserve cooperative norms, while fragmented or unilateral strategies significantly weaken the NSR’s viability. These findings suggest that the NSR reflects a conditional and institutionally mediated form of cooperation, providing an empirical illustration of how Arctic exceptionalism operates as a strategically negotiated and context-dependent governance outcome. By positioning Arctic shipping within broader debates on exceptionalism, conflict avoidance, and institutional resilience, this study contributes to understanding how climate dynamics and geopolitical tensions jointly reshape the prospects for peaceful governance in the Arctic.