Search

Abstract Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

The probiotic bacterium Escherichia coli Nissle 1917 (EcN) holds significant promise for use in clinical and biological industries. However, the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its benefits. In this study, we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and pMUT2. The non-essential elements were removed to create more stable derivatives pMUT1NR△ and pMUT2HBC△. Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinase III and the biosynthesis of ectoine. Compared to traditional antibiotic-dependent expression systems, our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

Abstract Objective The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. Methods This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut‐off value. The Kaplan–Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). Results The best cut‐off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional‐hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. Conclusion We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.

IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

Background: Angrogenetic alopecia (AGA) is one of the most prevalent hair loss disorders worldwide. The hair follicle stem cell (HFSC) is closely related to the formation of hair follicle (HF) structure and HF self-renewal. The activation of HFSC in AGA is critical for hair growth. Pilose antler has been reported to have hair growth-promoting activity, but the mechanism of action on AGA and HFSC has not been reported.Methods: We previously extracted an active component from the pilose antler known as PAEs. In this study, we conducted experiments using AGA mice and HFSC. The effects of PAEs on hair growth in AGA mice were firstly detected, and then the mechanisms of PAEs for AGA were predicted by integrating network pharmacology and de novo transcriptomics data of pilose antler. Finally, biological experiments were used to validate the molecular mechanism of PAEs in treating AGA both in vivo and in vitro.Results: It was found that PAEs promoted hair regrowth by accelerating the activation of anagen, delaying the anagen-catagen transition. It also alleviated the morphological changes, such as hair shortening, thinning, miniaturization, and HF number reduction, and regulated the hair regeneration process of four subtypes of hair. We further found that PAEs could promote the proliferation of HFSC, outer root sheath (ORS) cells, and hair bulb cells in AGA mice. We then integrated network pharmacology and pilose antler transcriptomics data to predict that the mechanism of PAEs treatment in AGA mice is closely related to the PI3K-AKT/Wnt-β-Catenin pathways. Subsequently, it was also verified that PAEs could activate both pathways in the skin of AGA mice. In addition, we found that PAEs perhaps increased the number of blood vessels around dermal papilla (DP) in experiments in vivo. Meanwhile, the PAEs stimulated the HFSC proliferation in vitro and activated the AKT and Wnt pathways. However, the proliferative activity of HFSC was inhibited after blocking the Wnt pathway and AKT activity.Conclusion: This study suggests that the hair growth-promoting effect of PAEs in AGA mice may be closely related to the stimulation of the AKT and Wnt pathways, which in turn activates the proliferation of HFSC.

Abstract The appearance of triboelectric nanogenerators (TENG) provides a promising energy technology for harvesting abundant water wave energy. Here, the design and fabrication of a swinging origami‐structured TENG (SO‐TENG) tailored specifically for water wave energy harvesting are presented. The design incorporates an oscillating structure weighted at the bottom, inducing reciprocating motion propelled by the inertia of passing water waves. This reciprocating motion efficiently converts mechanical into electrical energy through the origami structure. By employing origami as the monomer structure, the surface contact area between friction layers is enhanced, thereby optimizing output performance. the swinging structure, combined with the placement of heavy objects, enhances the folding and contact of the origami, allowing it to operate effectively in low‐frequency water wave environments. This configuration exhibits robust power generation capabilities, making it suitable for powering small electronic devices in water wave environments. Furthermore, when applied to metal corrosion protection, the SO‐TENG demonstrates notable efficacy. Compared to exposed Q235 carbon steel, Q235 carbon steel protected by SO‐TENG exhibits a significant reduction in open‐circuit potential drop, approximately 155 mV, indicative of superior anti‐corrosion properties. It lays a solid foundation for water wave energy collection and self‐powered metal corrosion protection in marine environments.

Abstract Contact resistance has become one of the main bottlenecks that hinder further improvement of mobility and integration density of organic field‐effect transistors (OFETs). Much progress has been made in reducing contact resistance by modifying the electrode/semiconductor interface and decreasing the crystal thickness, however, the development of new organic semiconductor materials with low contact resistance still faces many challenges. Here, 2,6‐bis‐phenylethynyl‐anthracene (BPEA) is found, which is a material that combines high mobility with low contact resistance. Single‐crystal BEPA OFETs with a thickness of ≈20 nm demonstrated high mobility of 4.52 cm2 V−1 s−1, contact resistance as low as 335 Ω cm, and band‐like charge transport behavior. The calculated compatibility of the EHOMO of BPEA with the work function of the Au electrode, and the decreased |EHOMO‐ΦAu| with the increase of external electric field intensity from source to gate both contributed to the efficient charge injection and small contact resistance. More intriguingly, p‐type BPEA as a buffer layer can effectively reduce the contact resistance, improve the mobility, and meanwhile inhibit the double‐slope electrical behavior of p‐channel 2,6‐diphenyl anthracene (DPA) single‐crystal OFETs.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

Evolutionary neural architecture search (ENAS) aims to automate the architecture design of deep neural networks (DNNs). In recent years, various ENAS algorithms have been proposed, and their effectiveness has been demonstrated. In practice, most ENAS methods based on genetic algorithms (GAs) use fixed-length encoding strategies because the generated chromosomes can be directly processed by the standard genetic operators (especially the crossover operator). However, the performance of existing ENAS methods with fixed-length encoding strategies can also be improved because the optimal depth is regarded as a known priori. Although variable-length encoding strategies may alleviate this issue, the standard genetic operators are replaced by the developed operators. In this paper, we proposed a framework to bridge this gap and to improve the performance of existing ENAS methods based on GAs. First, the fixed-length chromosomes were transformed into variable-length chromosomes with the encoding rules of the original ENAS methods. Second, an encoder was proposed to encode variable-length chromosomes into fixed-length representations that can be efficiently processed by standard genetic operators. Third, a decoder cotrained with the encoder was adopted to decode those processed high-dimensional representations which cannot directly describe architectures into original chromosomal forms. Overall, the performances of existing ENAS methods with fixed-length encoding strategies and variable-length encoding strategies have both improved by the proposed framework, and the effectiveness of the framework was justified through experimental results. Moreover, ablation experiments were performed and the results showed that the proposed framework does not negatively affect the original ENAS methods.

The short lifespan of active oxygen species and depressed O2 level during ferroptosis treatment in tumor cells weaken ferroptosis therapy. How to improve the utilization efficiency of active oxygen species generated in real time is pivotal for anticancer treatment. Herein, the tirapazamine (TPZ) loaded polydopamine-Fe nanoparticles (PDA-Fe-TPZ) was modified with unsaturated liposome (Lip), which was constructed to overcome the drawbacks of traditional ferroptosis therapy. The Lip@PDA-Fe-TPZ nanoliposomes can react with H2O2 to produce •OH by Fenton reaction, which then attacks Lip and transforms into radical intermediate (L•) and phospholipid peroxide radical (LOO•) to avoid the annihilation of •OH. The introduced Lip enhances lipid peroxidation and promotes oxygen consumption, resulting in increased hypoxia at tumor site. The introduced TPZ can be triggered by reductase in tumor cells under hypoxia, which can reduce to transient oxidative free radicals by reductase enzymes and destroy the structure of the surrounding biomacromolecules, thus achieving the synergistic treatment of ferroptosis and chemotherapy. In this work, we organically combined enhanced ferrroptosis with hypoxic activated chemotherapy to achieve efficient and specific tumor killing effect, which can sever as a promising treatment of cancer in the future.

IntroductionWhite Hypsizygus marmoreus is a popular edible mushroom. It is rich in nutrition and flavor but vulnerable to fungal disease, resulting in nutrient loss and aging.MethodsIn this study, the pathogenic fungus Trichoderma spp. BBP-6 and its antagonist Bacillus sp. 1–23 were isolated and identified. The negative effects caused by this pathogen were judged by detecting a series of changes in the infected white H. marmoreus. The effects of Bacillus sp. 1–23 on Trichoderma spp. BBP-6 and the infected white H. marmoreus were detected. The effect of Bacillus sp. 1–23 treatment combined with salicylic acid (SA) was also considered.ResultsThe results showed that Trichoderma spp. BBP-6 could affect the activities of antioxidant enzymes PAL, POD, CAT, SOD, GR, PPO, and APX to interfere with the stability of the white H. marmoreus antioxidant enzyme system and cause the mushroom severe browning and nutrition loss, as well as general quality deterioration. Bacillus sp. 1–23 could produce chitinase and chitosanase enzymes to inhibit Trichoderma spp. BBP-6 directly. SA reinforced this inhibitory. Bacillus sp. 1–23 alone or combined with SA could help white H. marmoreus from the Trichoderma spp. BBP-6 infection to effectively maintain nutrients, restore and stabilize the antioxidant system, and reduce the production of malondialdehyde, superoxide anion and hydrogen peroxide.DiscussionThus, such treatments could be considered potential methods to alleviate damage from disease and extend the shelf life of white H. marmoreus.

Microplastics (MPs) are environmental pollutants and can be inhaled by humans to threaten health. The lung tissue, responsible for the gas exchange between the body and the environment, is vulnerable to MPs exposure. However, from the perspective of cellular senescence, the effect of MPs on lung cells and tissues has not yet been deeply dissected. In this study, we reported that all the four typical MPs exhibited the significant biological effects in term of inducing senescence of human lung derived cells A549 and BEAS-2B in vitro. We further found that polyvinyl chloride (PVC) increased the reactive oxygen species (ROS) level in A549 cells and that PVC-induced senescent characteristics could be largely reversed by antioxidant treatment. Importantly, intratracheal instillation of PVC MPs in mice could effectively impair their physical function, induce the increased systemic inflammation level, cause the accumulation of senescent cells. Our study demonstrates that MPs induce senescence in human lung epithelial cells and mouse lungs by activating ROS signaling, and provides new insight into the potential pathogenesis of MPs on lung diseases.

Background: Acne vulgaris is a common skin disease that affects the pilosebaceous unit, and inflammation plays an important role. Chinese traditional medicine Tanreqing (TRQ) has been used in the field of dermatology to treat inflammatory diseases and has shown outstanding efficacy. The purpose of this study was to evaluate the potential advantages of TRQ on a mouse model of acne inflammation. Additionally, network pharmacology and transcriptome analysis were utilized to investigate the possible underlying mechanisms. Methods: The active compounds of TRQ were collected through TCMSP database and literature review, and the predicted targets of active compounds were obtained from Swiss Target Prediction. Acne targets were collected from the Gene Cards database and DisGeNET. Cytoscape v3.7.1 was used to build the ''compounds-targets'' network and PPI network and to obtain the core network. GO analysis and KEGG pathway annotation were performed on the core genes. The Illumina HiSeq sequencing platform was utilized to sequence mRNA from mouse skin tissue in acne areas. Differential gene expression analysis was conducted to identify genes that were affected by TRQ, and their associated biological functions and signaling pathways were analyzed. The transcriptomic and network pharmacology analyses were integrated to generate predictive results. Additionally, the efficacy of TRQ in treating acne was confirmed through H&E staining, and the predicted outcomes were verified through quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: The study's results indicate that 37 potential target genes were enriched in multiple signaling pathways, including the atherosclerosis, IL-17, and TNF signaling pathways, according to network pharmacology. In addition, 338 transcriptomic DEGs were found to be involved in various signaling pathways, including Cell adhesion molecules and the IL-17 signaling pathway.The combined analysis of these findings suggests that the IL-17 and TNF signaling pathways are the primary mechanisms by which TRQ exerts its anti-acne effects. H&E staining revealed that TRQ inhibited inflammatory cell infiltration in acne lesions and attenuated the inflammatory response in acne. Moreover, TRQ significantly suppressed key factors such as TNF-α, JNK2, IL-17A, C/EBPβ, IL-6, and IL-1β in the IL-17 and TNF signaling pathways. Furthermore, TRQ also demonstrated a significant inhibition in the expression of TNF-α and IL-1β in the skin tissues of acne vulgaris mice Conclusion: Our findings suggest that TRQ may effectively inhibit the IL-17/TNF signaling pathway by suppressing the expression of TNF-α and IL-1β, making it a potential candidate for the treatment of acne

Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM–receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism.

Interaction between transcription factors (TFs) and motifs is essential for gene regulation and the subsequent phenotype formation. Soybean (Glycine max) JAGGEED 1 (GmJAG1) is a key TF that controls leaf shape, seed number and flower size. To understand the GmJAG1 binding motifs, in this study, we performed the GmJAG1 DNA affinity purification sequencing (DAP-seq) experiment, which is a powerful tool for the de novo motif prediction method. Two new significant GmJAG1 binding motifs were predicted and the EMSA experiments further verified the ability of GmJAG1 bound to these motifs. The potential binding sites in the downstream gene promoter were identified through motif scanning and a potential regulatory network mediated by GmJAG1 was constructed. These results served as important genomic resources for further understanding the regulatory mechanism of GmJAG1.

The aim of this study was to investigate the clinical efficacy of combining pelvic floor neuromuscular stimulation treatment (NMES) with sodium hyaluronate in preventing intrauterine adhesions (IUA) following abortion. A total of 140 women who underwent artificial abortion were enrolled. The control group received only an intrauterine injection of sodium hyaluronate post-surgery, while the observation group received both the injection and daily pelvic floor NMES treatments, beginning on the day after the abortion. Monthly follow-ups on menstrual conditions were conducted for six months post-surgery. Fasting venous blood samples from both groups were collected on the second day post-abortion and the day after treatment. Transvaginal color Doppler ultrasound was used on the second day post-abortion and the 15th day post the first menstrual cycle to measure endometrial thickness, and the pulsatility and resistance indices of the endometrial spiral arteries. Over the six-month follow-up, the combination therapy group exhibited a notably lower IUA incidence compared to the control group (2.8% vs. 15.7%). Furthermore, combined treatment significantly expedited post-abortion menstrual recovery, reduced vaginal bleeding volume and duration (P < 0.001). It also increased endometrial thickness and reduced the endometrial spiral artery's pulsatility and resistance indices (P < 0.05). In addition, lower serum tumor necrosis factor alpha (TNF-α) and higher interleukin-10 (IL-10) were found in the observation group compared to the control group (P < 0.05). The combination therapy offers significant advantages in preventing and reducing IUA after abortion, resulting in a substantial reduction in IUA occurrence.

Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01–1.03), 1.04 (1.02–1.06), and 1.02 (1.00–1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05–1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01–1.03), 1.33 (1.18–1.50), and 1.07 (1.03–1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.

Health risks associated with acrylamide (ACR) or high-fat diet (HFD) exposure alone have been widely concerned in recent years. In a realistic situation, ACR and HFD are generally co-existence, and both are risk factors for the development of neurological diseases. The purpose of the present study was to investigate the combined effects of ACR and HFD on the motor nerve function. As a result, neurobehavioral tests and Nissl staining disclosed that long-term HFD exacerbated motor dysfunction and the damage of spinal cord motor neurons in ACR-exposed mice. Co-exposure of ACR and HFD resulted in morphological changes in neuronal mitochondria of the spinal cord, a significantly reduced mitochondrial subunits NDUFS1, UQCRC2, and MTCO1, released the mitochondrial DNA (mtDNA) into the cytoplasm, and promoted the production of reactive oxygen species (ROS). Combined exposure of HFD and ACR activated the calpain/CDK5/Drp1 axis and caused the mitochondrial excessive division, ultimately increasing MLKL-mediated necroptosis in spinal cord motor neurons. Meanwhile, HFD significantly exacerbated ACR-induced activation of NFkB, NLRP3 inflammasome, and cGAS-STING pathway. Taken together, our findings demonstrated that combined exposure of ACR and HFD aggravated the damage of spinal cord motor neurons via neuroinflammation and necroptosis signaling pathway, pointing to additive effects in mice than the individual stress effects.

TR2 and TR4 (NR2C1 and NR2C2, respectively) are evolutionarily conserved nuclear orphan receptors capable of binding direct repeat sequences in a stage-specific manner. Like other nuclear receptors, TR2 and TR4 possess important roles in transcriptional activation or repression with developmental stage and tissue specificity. TR2 and TR4 bind DNA and possess the ability to complex with available cofactors mediating developmental stage-specific actions in primitive and definitive erythrocytes. In erythropoiesis, TR2 and TR4 are required for erythroid development, maturation, and key erythroid transcription factor regulation. TR2 and TR4 recruit and interact with transcriptional corepressors or coactivators to elicit developmental stage-specific gene regulation during hematopoiesis.

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation’s impact on stem cell-mediated alveolar regeneration.

Polarization imaging is a label-free and non-invasive technique that is sensitive to microstructure and suitable for probing the microstructure of living tissues. However, obtaining deep-layer information from tissues has been a challenge for optical techniques. In this work, we used tissue optical clearing (TOC) to increase optical penetration depth and characterize the layered structures of tissue samples. Different tissue phantoms were constructed to examine changes in the polarization features of the layered structure during the TOC process. We found that depolarization and anisotropy parameters were able to distinguish between single-layer and double-layer phantoms, reflecting microstructural information from each layer. We observed changes in polarization parameter images during the TOC process and, by analyzing different regions of the images, explained the sensitivity of these parameters to double-layer structures and analyzed the influence of oblique incident illumination. Finally, we conducted TOC experiments on living skin samples, leveraging the experience gained from phantom experiments to identify the double-layer structure of the skin and extract features related to layered structures. The results show that the combination of backscattering polarization imaging and tissue optical clearing provides a powerful tool for the characterization of layered samples.

Owing to limited research on the interactions between cropland vegetation and climate and irrigation, this study used the normalized difference vegetation index (NDVI) as a cropland vegetation indicator to describe vegetation dynamics. Potential evapotranspiration (PET) was calculated using the Penman–Monteith equation. A partial correlation analysis and a Pearson correlation coefficient were used to determine the spatial response mechanisms of cropland vegetation to different climatic factors and irrigation in China for the period 1985–2015. The results show that different climatic factors (precipitation, PET, and water deficits) display positive correlations with cropland vegetation in China. A stronger correlation was observed between cropland vegetation and meteorological factors in northern China compared to the southern parts; the response time of NDVI values of croplands to precipitation was observed to be short-term (1 to 3 months) and long-term (3 to 6 months) in northern and southern regions, respectively. In contrast, the response time of NDVI values of croplands to PET displayed a complex spatial heterogeneity. Most of the cropland vegetation and the areas with the highest potential crop yields were located in the eastern part of China; these areas also require higher levels of irrigation, which benefits the potential crop yields. This study can provide a better understanding of the agricultural ecosystems and formulate strategies for food security.