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Diabetic kidney disease (DKD), as the most common complication of diabetes mellitus (DM), is the major cause of end-stage renal disease (ESRD). Renal interstitial fibrosis is a crucial metabolic change in the late stage of DKD, which is always considered to be complex and irreversible. In this review, we discuss the pathological mechanisms of diabetic renal fibrosis and discussed some signaling pathways that are closely related to it, such as the TGF-β, MAPK, Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch pathways. The cross-talks among these pathways were then discussed to elucidate the complicated cascade behind the tubulointerstitial fibrosis. Finally, we summarized the new drugs with potential therapeutic effects on renal fibrosis and listed related clinical trials. The purpose of this review is to elucidate the mechanisms and related pathways of renal fibrosis in DKD and to provide novel therapeutic intervention insights for clinical research to delay the progression of renal fibrosis.

During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4+ and CD8+ T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4+ T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.

Carbonyl-containing metabolites widely exist in biological samples and have important physiological functions. Thus, accurate and sensitive quantitative analysis of carbonyl-containing metabolites is crucial to provide insight into metabolic pathways as well as disease mechanisms. Although reversed phase liquid chromatography electrospray ionization mass spectrometry (RPLC-ESI-MS) is widely used due to the powerful separation capability of RPLC and high specificity and sensitivity of MS, but it is often challenging to directly analyze carbonyl-containing metabolites using RPLC-ESI-MS due to the poor ionization efficiency of neutral carbonyl groups in ESI. Modification of carbonyl-containing metabolites by a chemical derivatization strategy can overcome the obstacle of sensitivity; however, it is insufficient to achieve accurate quantification due to instrument drift and matrix effects. The emergence of stable isotope-coded derivatization (ICD) provides a good solution to the problems encountered above. Thus, LC-MS methods that utilize ICD have been applied in metabolomics including quantitative targeted analysis and untargeted profiling analysis. In addition, ICD makes multiplex or multichannel submetabolome analysis possible, which not only reduces instrument running time but also avoids the variation of MS response. In this review, representative derivatization reagents and typical applications in absolute quantification and submetabolome profiling are discussed to highlight the superiority of the ICD strategy for detection of carbonyl-containing metabolites.

Facing the growing awareness of food safety hazards and related issues associated with premade dishes, this study incorporated health consciousness and social trust into the benefit–risk analysis model to examine the determinants of risk acceptance for premade dishes, and assess the stability and dynamic evolution of risk acceptance pathways before and after media exposure. In total, 911 Chinese consumers (383 in Period I and 528 in Period II) were collected through an online questionnaire and analyzed using structural equation modeling in this study. The results indicated that perceived benefits were the prominent mediator that outweighed perceived risks in explaining consumers’ risk acceptance of premade dishes. Social trust enhanced perceived benefits while simultaneously amplifying perceived risks, as well as positively affecting consumers’ risk acceptance through perceived benefits. Health consciousness, as individuals’ intrinsic motivation, positively affects risk acceptance through social trust and perceived benefits. Comparative analysis across two periods demonstrated a dynamic shift: the significantly negative impact of perceived risks on risk acceptance diminished while the dominance of perceived benefits substantially strengthened. This study provides insights into relevant theories on risk acceptance and contributes to policy development regarding food safety in the PD industry. Plain Language Summary Factors and Dynamic Evolution Influencing Chinese Consumers’ Risk Acceptance Towards pre-made Meals with The Controversy of Food Safety issues The way people feel about the safety of food is a mix of thinking about how good it is for them and how much they like it, and how safe they think it is. When it comes to pre-made meals in schools and canteens, this becomes even more complicated because there are arguments about whether they’re nutritious, fresh, safe or not. To understand factors and dynamic evolution influencing Chinese consumers’ risk acceptance towards pre-made meals with potential risks of premade dishes (like food safety concerns), especially as awareness of these issues grows, we totally surveyed 911 consumers at two different periods to see how their views changed, particularly after media coverage. The study found that the benefits consumers see in premade dishes (like convenience) are a much bigger factor in their acceptance than the risks they perceive. Essentially, the good things outweigh the worries for most people. Social trust (trust in companies, regulators, etc.) plays a key role: it increases the perceived benefits and makes people more aware of risks. However, overall, social trust still leads to greater acceptance because it boosts the perception of benefits so strongly. Health consciousness (personal concern about health) also promotes acceptance, but it works indirectly by increasing social trust and perceived benefits. Comparing the two survey periods showed that consumers shifted from simply avoiding risks to actively weighing benefits. This change happened because premade dishes improved, companies better met consumer needs, people became more familiar with the products, and busier lifestyles increased demand for convenience. In short, when it comes to premade dishes, consumers focus more on the convenience and other benefits than the risks, especially as time passes. Trust in the system and personal health concerns drive this focus on benefits. These insights can help policymakers and the premade dish industry address safety concerns effectively.

Backgroud Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. Results Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients ( p  < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. Conclusions This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE.

Arsenic is an essential dopant in conventional silicon-based semiconductors and emerging phase-change memory (PCM), yet the detailed functional mechanism is still lacking in the latter. Here, we fabricate chalcogenide-based ovonic threshold switching (OTS) selectors, which are key units for suppressing sneak currents in 3D PCM arrays, with various As concentrations. We discovered that incorporation of As into GeS brings >100 °C increase in crystallization temperature, remarkably improving the switching repeatability and prolonging the device lifetime. These benefits arise from strengthened As-S bonds and sluggish atomic migration after As incorporation, which reduces the leakage current by more than an order of magnitude and significantly suppresses the operational voltage drift, ultimately enabling a back-end-of-line-compatible OTS selector with >12 MA/cm 2 on-current, ~10 ns speed, and a lifetime approaching 10 10 cycles after 450 °C annealing. These findings allow the precise performance control of GeSAs-based OTS materials for high-density 3D PCM applications. Spin defects in semiconductors are promising for quantum technologies but understanding of defect formation processes in experiment remains incomplete. Here the authors present a computational protocol to study the formation of spin defects at the atomic scale and apply it to the divacancy defect in SiC.

Lung cancer is a devastating disease that remains a top cause of cancer mortality. Despite improvements with targeted and immunotherapies, the majority of patients with lung cancer lack effective therapies, underscoring the need for additional treatment approaches. Genomic studies have identified frequent alterations in components of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A . To understand the mechanisms of tumorigenesis driven by mutations in this complex, we developed a genetically engineered mouse model of lung adenocarcinoma by ablating Smarca4 in the lung epithelium. We demonstrate that Smarca4 acts as a bona fide tumor suppressor and cooperates with p53 loss and Kras activation. Gene expression analyses revealed the signature of enhanced oxidative phosphorylation (OXPHOS) in SMARCA4 mutant tumors. We further show that SMARCA4 mutant cells have enhanced oxygen consumption and increased respiratory capacity. Importantly, SMARCA4 mutant lung cancer cell lines and xenograft tumors have marked sensitivity to inhibition of OXPHOS by a novel small molecule, IACS-010759, that is under clinical development. Mechanistically, we show that SMARCA4 -deficient cells have a blunted transcriptional response to energy stress creating a therapeutically exploitable synthetic lethal interaction. These findings provide the mechanistic basis for further development of OXPHOS inhibitors as therapeutics against SWI/SNF mutant tumors. SMARCA4 loss in non-small-cell lung cancer creates a metabolic dependency on oxidative phosphorylation that can be targeted using a new small-molecule inhibitor.

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI. The heterogeneous characters of fibrotic scars after spinal cord injury remains unclear. Here, the authors show the heterogeneous distribution, source and function of meningeal fibroblasts and perivascular fibroblasts in fibrotic scars.

Distributed Acoustic Sensing (DAS) is a novel technology that uses fiber optics to sense and monitor vibrations. It has demonstrated immense potential for various applications, including seismology research, traffic vibration detection, structural health inspection, and lifeline engineering. DAS technology transforms long sections of fiber optic cables into a high−density array of vibration sensors, providing exceptional spatial and temporal resolution for real−time monitoring of vibrations. Obtaining high−quality vibration data using DAS requires a robust coupling between the fiber optic cable and the ground layer. The study utilized the DAS system to detect vibration signals generated by vehicles operating on the campus road of Beijing Jiaotong University. Three distinct deployment methods were employed: the uncoupled fiber on the road, the underground communication fiber optic cable ducts, and the cement−bonded fixed fiber optic cable on the road shoulder, and compared for their outcomes. Vehicle vibration signals under the three deployment methods were analyzed using an improved wavelet threshold algorithm, which was verified to be effective. The results indicate that for practical applications, the most effective deployment method is the cement−bonded fixed fiber optic cable on the road shoulder, followed by the uncoupled fiber on the road, and the underground communication fiber optic cable ducts are the least effective. This has important implications for the future development of DAS as a tool for various fields.

Insects constitute a very important part of the global ecosystem and include pollinators, disease vectors, and agricultural pests, all with pivotal influence on society. Monitoring and control of such insects has high priority, and automatic systems are highly desirable. While capture and analysis by biologists constitute the gold standard in insect identification, optical and laser techniques have the potential for high-speed detection and automatic identification based on shape, spectroscopic properties such as reflectance and fluorescence, as well as wing-beat frequency analysis. The present paper discusses these approaches, and in particular presents a novel method for automatic identification of mosquitos based on image analysis, as the insects enter a trap based on a combination of chemical and suction attraction. Details of the analysis procedure are presented, and selectivity is discussed. An accuracy of 93% is achieved by our proposed method from a data set containing 122 insect images (mosquitoes and bees). As a powerful and cost-effective method, we finally propose the combination of imaging and wing-beat frequency analysis in an integrated instrument.