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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.

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a subtype of chronic rhinosinusitis (CRS) that is associated with the nasal cavity and sinus polyps, elevated levels of eosinophils, and dysregulated immune responses to environmental triggers. The underlying cause of ECRSwNP is not well understood, and few studies have focused on the unique features of this subtype of CRS. Our study integrated proteomic and transcriptomic data with multi‐omic bioinformatics analyses. We collected nasal polyps from three ECRSwNP patients and three control patients and identified 360 differentially expressed (DE) proteins, including 119 upregulated and 241 downregulated proteins. Functional analyses revealed several significant associations with ECRSwNP, including focal adhesion, hypertrophic cardiomyopathy, and extracellular matrix (ECM)–receptor interactions. Additionally, a protein–protein interaction (PPI) network revealed seven hub proteins that may play crucial roles in the development of ECRSwNP. We also compared the proteomic data with publicly available transcriptomic data and identified a total of 1077 DE genes. Pathways enriched by the DE genes involved angiogenesis, positive regulation of cell motility, and immune responses. Furthermore, we investigated immune cell infiltration and identified biomarkers associated with eosinophil and M2 macrophage infiltration using CIBERSORT and Weighted Gene Correlation Network Analysis (WGCNA). Our results provide a more complete picture of the immune‐related mechanisms underlying ECRSwNP, which could contribute to the development of more precise treatment strategies for this condition.

Abstract Background The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis is commonly observed in gastric cancer, while effective therapeutic targets for the Hippo/YAP axis are lacking. Identification of reliable drug targets and the underlying mechanisms that could inhibit the activity of the Hippo/YAP axis and gastric cancer progression is urgently needed. Methods We used several gastric cancer cell lines and xenograft models and performed immunoblotting, qPCR, and in vivo studies to investigate the function of CXCR7 in gastric cancer progression. Results In our current study, we demonstrate that the membrane receptor CXCR7 (C-X-C chemokine receptor 7) is an important modulator of the Hippo/YAP axis. The activation of CXCR7 could stimulate gastric cancer cell progression through the Hippo/YAP axis in vitro and in vivo, while pharmaceutical inhibition of CXCR7 via ACT-1004–1239 could block tumorigenesis in gastric cancer. Molecular studies revealed that the activation of CXCR7 could dephosphorylate YAP and facilitate YAP nuclear accumulation and transcriptional activation in gastric cancer. CXCR7 functions via G-protein Gαq/11 and Rho GTPase to activate YAP activity. Interestingly, ChIP assays showed that YAP could bind to the promoter region of CXCR7 and facilitate its gene transcription, which indicates that CXCR7 is both the upstream signalling and downstream target of the Hippo/YAP axis in gastric cancer. Conclusion In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer.

Exposure to carbon disulfide (CS2) is a recognized risk factor in the pathogenesis of Parkinson’s disease, yet the underlying mechanisms of deleterious effects on mitochondrial integrity have remained elusive. Here, through establishing CS2 exposure models in rat and SH-SY5Y cells, we demonstrated that highly expressed α-synuclein (α-Syn) is transferred to mitochondria via membrane proteins such as Tom20 and leads to mitochondrial dysfunction and mitochondrial oxidative stress, which ultimately causes neuronal injury. We first found significant mitochondrial damage and oxidative stress in CS2-exposed rat midbrain and SH-SY5Y cells and showed that mitochondrial oxidative stress was the main factor of mitochondrial damage by Mitoquinone intervention. Further experiments revealed that CS2 exposure led to the accumulation of α-Syn in mitochondria and that α-Syn co-immunoprecipitated with mitochondrial membrane proteins. Finally, the use of an α-Syn inhibitor (ELN484228) and small interfering RNA (siRNA) effectively mitigated the accumulation of α-Syn in neurons, as well as the inhibition of mitochondrial membrane potential, caused by CS2 exposure. In conclusion, our study identifies the translocation of α-Syn to mitochondria and the impairment of mitochondrial function, which has important implications for the broader understanding and treatment of neurodegenerative diseases associated with environmental toxins.

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.

Immunogenic cell death (ICD) is essential for the activation of immune system against cancer. We aimed to investigate the efficacy of endoplasmic reticulum (ER)-associated protein degradation (ERAD) inhibitors (EerI and NMS-873) in enhancing radiation-induced ICD in esophageal cancer (EC). EC cells were administered with ERAD inhibitors, radiation therapy (RT), and the combination treatment. ICD hallmarks including calreticulin (CALR), adenosine triphosphate (ATP), and high mobility group protein B1 (HMGB1) were detected. The efficacy of ERAD inhibitors combined with RT in stimulating ICD was analyzed. Additionally, the role of ICD hallmarks in immune cell infiltration and patient survival was investigated. Inhibiting ERAD pathways was able to stimulate ICD component emission from dying EC cells in a dose-dependent pattern. Radiation-induced ICD was significantly increased after high doses RT (≥10 Gy). ERAD inhibitor combined with moderate dose RT (≥6 Gy) was capable of stimulating increased ICD in EC cells. Dual therapy could elicit the antitumor immune response by enhancing dendritic cells maturation and phagocytosis. Further investigation revealed a significant correlation between CALR and tumor-infiltrating immune cells. Low expression of ATP and HMGB1 and high expression of CALR were associated with favorable survival in patients with EC. The immunogenicityof EC can be enhanced by ERAD inhibitors combined with moderate doses of RT. ICD hallmark genes, especially CALR, are correlated to immune cell infiltration and clinical outcomes in EC. The present results demonstrated an important method to improve the immunogenicity of EC cells for enhanced antitumor immune response.

Abstract It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50–400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60–100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P

Abstract Background Transfer (t)RNA-derived small RNA (tsRNA), generated from precursor or mature tRNA, is a new type of small non-coding RNA (sncRNA) that has recently been shown to play a vital role in human cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods We elucidated the expression profiles of tsRNAs in four paired LSCC and non-neoplastic tissues by sequencing and verified the sequencing data by quantitative real-time PCR (qRT–PCR) of 60 paired samples. The tyrosine-tRNA derivative tRFTyr was identified as a novel oncogene in LSCC for further study. Loss-of-function experiments were performed to evaluate the roles of tRFTyr in tumorigenesis of LSCC. Mechanistic experiments including RNA pull-down, parallel reaction monitoring (PRM) and RNA immunoprecipitation (RIP) were employed to uncover the regulatory mechanism of tRFTyr in LSCC. Results tRFTyr was significantly upregulated in LSCC samples. Functional assays showed that knockdown of tRFTyr significantly suppressed the progression of LSCC. A series of mechanistic studies revealed that tRFTyr could enhance the phosphorylated level of lactate dehydrogenase A (LDHA) by interacting with it. The activity of LDHA was also activated, which induced lactate accumulation in LSCC cells. Conclusions Our data delineated the landscape of tsRNAs in LSCC and identified the oncogenic role of tRFTyr in LSCC. tRFTyr could promote lactate accumulation and tumour progression in LSCC by binding to LDHA. These findings may aid in the development of new diagnostic biomarkers and provide new insights into therapeutic strategies for LSCC.

Objective: To investigate the radiation response and proteomic profiling of esophageal epithelial cells cultured under physioxia and normoxia. Methods: The human immortalized normal esophageal epithelial cell line SHEE cells were cultured under normoxia (21%) and physioxia (4%), respectively. A clonogenic assay was performed to evaluate the radiation response of SHEE cells. Cellular proteomic profiling of SHEE cells maintained under physioxia and normoxia was conducted to determine the differentially expressed proteins. Then, the identified differentially expressed proteins were validated by Western blot. Results: SHEE cells exposed to normoxia showed an increased radiation response compared to physioxia (irradiation dose ≥10 ​Gy, P< 0.05). Over 1200 non-redundant proteins were identified in the collected samples. Protein expression was compared between physioxia and normoxia, 42 proteins were downregulated and 45 proteins upregulated, in which oxidative phosphorylation was the most significantly enriched pathway. When cells were cultured under normoxia conditions, the induction of antioxidant genes appeared to contribute to form a phenotype adapted to the environment with high oxygen-content. Further analysis validated NRF2, BIP, VCP, SOD1, and YAP1 were the key regulators of this phenotype. Conclusions: Compared with physioxia, normoxic cell culture condition can enhance the radiation response. This study could stimulate in vivo microenvironment, and provide a basis for radiation-induced normal tissue damage.

Abstract Background Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. Methods Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. Results Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. Conclusions We developed a DLAT-based model to predict patients’ clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy.

Abstract Gray mold, caused by Botrytis cinerea, poses a significant threat to the strawberry industry worldwide. B. cinerea is a high-risk pathogen in the sense of fungicide resistance. The sensitivities of B. cinerea isolates collected from Zhejiang Province, China, to the succinate dehydrogenase inhibitors (SDHIs) boscalid and Y12196 were determined based on discriminatory dose or 50% effective concentration (EC50). Of the 42 isolates collected in 2018, 15 were resistant to boscalid (35.7%), and 3 were resistant to Y12196 (7.1%). Among the 84 isolates collected in 2019, the EC50 values for boscalid ranged from 0.097 to 54.162 mg/L, while the EC50 values for Y12196 ranged from 0.284 to 20.147 mg/L. Sequence analysis showed that the B. cinerea isolates carrying P225F (proline → phenylalanine) and N230I (asparagine → isoleucine) mutations in SDH subunit B exhibited cross-resistance between boscalid and Y12196. However, boscalid-resistant isolates with a point mutation at position 272 of SDH B (H272R, histidine → arginine) were more sensitive to Y12196. Consistent with this, Y12196, but not boscalid, could successfully inhibit the growth of B. cinerea carrying the H272R mutation (BcSDHB−H272R) on detached strawberries and leaves. Molecular docking simulations further revealed that the hydrogen bonds and π-π interactions were formed between Y12196 and BcSDHB−H272R, but not between boscalid and BcSDHB−H272R, explaining why the boscalid-resistant B. cinerea H272R mutant isolates were sensitive to Y12196. Together, our results suggested that Y12196 could effectively control boscalid resistance associated with the H272R mutation.

Abstract Bacterial symbioses allow annelids to colonise extreme ecological niches, such as hydrothermal vents and whale falls. Yet, the genetic principles sustaining these symbioses remain unclear. Here, we show that different genomic adaptations underpin the symbioses of phylogenetically related annelids with distinct nutritional strategies. Genome compaction and extensive gene losses distinguish the heterotrophic symbiosis of the bone-eating worm Osedax frankpressi from the chemoautotrophic symbiosis of deep-sea Vestimentifera. Osedax’s endosymbionts complement many of the host’s metabolic deficiencies, including the loss of pathways to recycle nitrogen and synthesise some amino acids. Osedax’s endosymbionts possess the glyoxylate cycle, which could allow more efficient catabolism of bone-derived nutrients and the production of carbohydrates from fatty acids. Unlike in most Vestimentifera, innate immunity genes are reduced in O. frankpressi, which, however, has an expansion of matrix metalloproteases to digest collagen. Our study supports that distinct nutritional interactions influence host genome evolution differently in highly specialised symbioses.

Modern technological lifestyles promote allergic diseases, especially food allergies. The underlying molecular mechanisms remain to be uncovered. Protein acetylation is one of the most important post-translational modifications, and it is involved in regulating multiple body metabolic processes. This study aimed to clarify the effects of a high-fat diet (HFD) on allergy risk and the underlying mechanisms. Four-week-old male C57BL/6J mice were randomly divided into two groups and fed a normal fat diet (NFD) or HFD for 24 weeks. Then, serum lipids were measured, and skeletal muscle was collected for acetylome analysis. Compared with the findings in the NFD group, HFD-fed mice were obese and hyperlipidemic. Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups. Among these, eight acetylated proteins were upregulated in the HFD group. In addition, 13 and 11 proteins were acetylated only in the HFD group and NFD group, respectively. These proteins were mainly involved in regulating energy metabolism and mitochondrial function. This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

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.

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. The Hippo signaling pathway has emerged as a significant suppressive pathway for hepatocellular carcinogenesis. The core components of the Hippo pathway constitute a kinase cascade, which inhibits the functional activation of YAP/TAZ. Interestingly, the overactivation of YAP/TAZ is commonly observed in hepatocellular carcinoma, although the inhibitory kinase cascade of the Hippo pathway is still functional. Recent studies have indicated that the ubiquitin‒proteasome system also plays important roles in modulating Hippo signaling activity. Our DUB (deubiquitinase) siRNA screen showed that USP1 is a critical regulator of Hippo signaling activity. Analysis of TCGA data demonstrated that USP1 expression is elevated in HCC and associated with poor survival in HCC patients. RNA sequencing analysis revealed that USP1 depletion affects Hippo signaling activity in HCC cell lines. Mechanistic assays revealed that USP1 is required for Hippo/TAZ axis activity and HCC progression. USP1 interacted with the WW domain of TAZ, which subsequently enhanced TAZ stability by suppressing K11-linked polyubiquitination of TAZ. Our study identifies a novel mechanism linking USP1 and TAZ in regulating the Hippo pathway and one possible therapeutic target for HCC.

Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.

Abstract Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus. Interleukin-18, an inflammasome-induced cytokine, has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown. Based on a screening panel, IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19. Supporting clinical data, administration of SARS-CoV-2 Spike 1 (S1) glycoprotein or receptor-binding domain (RBD) proteins into human angiotensin-converting enzyme 2 (hACE2) transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation (pNF-κB) and cardiopulmonary-derived IL-18 and NLRP3 expression. IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1- or RBD-exposed hACE2 mice. Through in vivo and in vitro work, both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species. Enhancing mitophagy prevented Spike protein-mediated IL-18 expression. Moreover, IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability. Overall, the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.

A two-year field trial was conducted to investigate the effects of partial substitution of chemical fertilizer (CF) by Trichoderma biofertilizer (TF) on nitrogen (N) use efficiency and associated mechanisms in wolfberry (Lycium chinense) in coastal saline land. As with plant biomass and fruit yield, apparent N use efficiency and plant N accumulation were also higher with TF plus 75% CF than 100% CF, indicating that TF substitution promoted plant growth and N uptake. As a reason, TF substitution stabilized soil N supply by mitigating steep deceases in soil NH4+-N and NO3–N concentrations in the second half of growing seasons. TF substitution also increased carbon (C) fixation according to higher photosynthetic rate (Pn) and stable 13C abundance with TF plus 75% CF than 100% CF. Importantly, leaf N accumulation significantly and positively related with Pn, biomass, and fruit yield, and structural equation modeling also confirmed the importance of the causal relation of N accumulation coupled with C fixation for biomass and yield formation. Consequently, physiological and agronomical N use efficiencies were significantly higher with TF plus 75% CF than 100% CF. Overall, partial substitution of CF by TF improved N use efficiency in wolfberry in coastal saline land by stabilizing soil N supply and coupling N accumulation with C fixation.

Summary: Exposure to carbon disulfide (CS2) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS2 exposure. Taken together, our results demonstrate that CS2-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

Scarring is one of the biggest areas of unmet need in the long-term success of glaucoma filtration surgery. Quantitative evaluation of the scar tissue and the post-operative structure with micron scale resolution facilitates development of anti-fibrosis techniques. However, the distinguishment of conjunctiva, sclera and the scar tissue in the surgical area still relies on pathologists’ experience. Since polarized light imaging is sensitive to anisotropic properties of the media, it is ideal for discrimination of scar in the subconjunctival and episcleral area by characterizing small differences between proportion, organization and the orientation of the fibers. In this paper, we defined the conjunctiva, sclera, and the scar tissue as three target tissues after glaucoma filtration surgery and obtained their polarization characteristics from the tissue sections by a Mueller matrix microscope. Discrimination score based on parameters derived from Mueller matrix and machine learning was calculated and tested as a diagnostic index. As a result, the discrimination score of three target tissues showed significant difference between each other ([Formula: see text]). The visualization of the discrimination results showed significant contrast between target tissues. This study proved that Mueller matrix imaging is effective in ocular scar discrimination and paves the way for its application on other forms of ocular fibrosis as a substitute or supplementary for clinical practice.

Summary: Studying gene function in T cells is crucial for understanding physiology and disease pathogenesis. Here, we provide a protocol to examine the role of specific genes in CD4+ T cell differentiation in the intestine. We describe steps for isolating naïve CD4+ T cells from mouse spleens and transferring them to recipient mice. We detail procedures to isolate lamina propria cells and analyze CD4+ T subsets using flow cytometry. This protocol is useful in the study of mucosal immune functions.For complete details on the use and execution of this protocol, please refer to Duan et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

IntroductionThe aim of this study is to demonstrate the relevance of primary acute angle closure (APAC) and COVID-19 infection, compare the demographic features and manifestations between COVID-19 positive and negative patients with APAC, and infer the underlying mechanism.MethodsThis study is based on all patients diagnosed with APAC at the glaucoma center of Eye, Ear, Nose and Throat Hospital of Fudan University (Fenyang road center) from 15th December 2022 to 11th January 2023. Totally 171 APAC cases were categorized into COVID-19 positive and negative group. Demographic features and final treatment level of the patients were compared between the two groups. Clinical manifestations, intraocular pressure, and anterior chamber configuration were also compared between the two groups.ResultsIn the COVID-19 positive group, the number of cases with APAC onset spiked in 22nd December 2022, which coincided with the spike of COVID-19 antigen positive people. Compared to the COVID-19 negative group, COVID-19 positive APAC patients were younger with a lower percentage of APAC history. Additionally, more eyes of COVID-19 positive APAC patients showed keratic precipitates. COVID-19 positive eyes had significantly larger anterior chamber depth with a more dilated pupil. Therefore, COVID-19 infection could probably act as a triggering factor of APACDiscussionThe onset of APAC might be accelerated by COVID-19 infection for patients with younger age and milder anatomical configuration. Additionally, COVID-19 related APAC cases might have a more abrupt and fierce onset. Ophthalmic emergent services should not be neglected during the epidemic period.

Cognitive impairment is typically reflected in the time and frequency variations of electroencephalography (EEG). Integrating time-domain and frequency-domain analysis methods is essential to better understand and assess cognitive ability. Timely identification of cognitive levels in early Parkinson’s disease (ePD) patients can help mitigate the risk of future dementia. For the investigation of the brain activity and states related to cognitive levels, this study recruited forty ePD patients for EEG microstate analysis, including 13 with mild cognitive impairment (MCI) and 27 without MCI (control group). To determine the specific frequency band on which the microstate analysis relies, a deep learning framework was employed to discern the frequency dependence of the cognitive level in ePD patients. The input to the convolutional neural network consisted of the power spectral density of multi-channel multi-point EEG signals. The visualization technique of gradient-weighted class activation mapping was utilized to extract the optimal frequency band for identifying MCI samples. Within this frequency band, microstate analysis was conducted and correlated with the Montreal Cognitive Assessment (MoCA) Scale. The deep neural network revealed significant differences in the 1-11.5Hz spectrum of the ePD-MCI group compared to the control group. In this characteristic frequency band, ePD-MCI patients exhibited a pattern of global microstate disorder. The coverage rate and occurrence frequency of microstate A and D increased significantly and were both negatively correlated with the MoCA scale. Meanwhile, the coverage, frequency and duration of microstate C decreased significantly and were positively correlated with the MoCA scale. Our work unveils abnormal microstate characteristics in ePD-MCI based on time-frequency fusion, enhancing our understanding of cognitively related brain dynamics and providing electrophysiological markers for ePD-MCI recognition.

Abstract Disruption of the microbial structure of intestinal bacteria due to a high‐fat diet (HFD) is closely associated with metabolic disorders, such as obesity and type 2 diabetes. Probiotics are known to modulate the gut microbiota; therefore, we demonstrated the capability of Lactobacillus paracasei N1115 (LC‐N1115) to attenuate obesity. Four‐week‐old male C57BL/6J mice were fed a HFD for 12 weeks to induce obesity and were then randomized to supplemented placebo or LC‐N1115 treatment group for another 12 weeks. LC‐N1115 treatment reduced weight gain and liver fat accumulation as well as triglyceride, total cholesterol, and low‐density lipoprotein cholesterol levels. The administration of LC‐N1115 suppressed the expression of fatty acid synthase, interleukin‐1 β, and toll‐like receptor 4. Notably, the operational taxonomic units that negatively and positively correlated with the obesity phenotypes were enriched and reduced, respectively, in the LC‐N1115 treatment group. These results indicate that LC‐N1115 attenuates obesity by modulating the gut microbiota and the expression of lipid synthesis and proinflammatory cytokine genes.

Abstract Autophagy is a multi-step catabolic process that delivers cellular components to lysosomes for degradation and recycling. The dysregulation of this precisely controlled process disrupts cellular homeostasis and leads to many pathophysiological conditions. The mechanistic target of rapamycin (mTOR) is a central nutrient sensor that integrates growth signals with anabolism to fulfil biosynthetic and bioenergetic requirements. mTOR nucleates two distinct evolutionarily conserved complexes (mTORC1 and mTORC2). However, only mTORC1 is acutely inhibited by rapamycin. Consequently, mTORC1 is a well characterized regulator of autophagy. While less is known about mTORC2, the availability of acute small molecule inhibitors and multiple genetic models has led to increased understanding about the role of mTORC2 in autophagy. Emerging evidence suggests that the regulation of mTORC2 in autophagy is mainly through its downstream effector proteins, and is variable under different conditions and cellular contexts. Here, we review recent advances that describe a role for mTORC2 in this catabolic process, and propose that mTORC2 could be a potential clinical target for the treatment of autophagy-related diseases. Video abstract Graphical abstract

Abstract Exosomes are a new way of the communication between the tumor cell and macrophage in the micro-environment. The macrophage can be induced to different phenotypes according to the different tumors. In the present study, long-chain noncoding RNA HOTAIR (lncRNA HOTAIR) was highly expressed in LSCC and exosomes. The pathway of exosomal lncRNA HOTAIR inducing macrophage to M2 polarization in the LSCC was investigated. The carcinoma tissues and adjacent tissues were collected from 104 LSCC cases, and the positive relationship between CD163-/CD206-M2 macrophage infiltration and clinical phase, lymph node spreading and pathological phase in LSCC was observed. To examine the role of exosomal lncRNA HOTAIR, macrophages were co-cultured with LSCC-exosomes of high lncRNA HOTAIR expression or transferred with HOTAIR mimics. It was suggested that exosomal lncRNA HOTAIR can induce macrophages to M2 polarization by PI3K/p-AKT/AKT signaling pathway. Furthermore, exo-treated M2 macrophages facilitate the migration, proliferation, and EMT of LSCC.

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.

Polydopamine (PDA) as a melanin-like biomimetic material with excellent biocompatibility, full spectrum light absorption capacity and antioxidation property has been extensively applied in the biomedical field. Based on the high reactivity of dopamine (DA), exploiting new strategies to fabricate novel PDA-based nano-biomaterials with controllable size and improved performance is valuable and desirable. Herein, we reported a facile way to synthesize pyrrole-doped polydopamine-pyrrole nanoparticles (PDA-nPY NPs) with tunable size and enhanced near-infrared (NIR) absorption capacity through self-oxidative polymerization of DA with PY in an alkaline ethanol/H2O/NH4OH solution. The PDA-nPY NPs maintain excellent biocompatibility and surface reactivity as PDA. By regulating the volume of added PY, PDA-150PY NPs with a smaller size (

The feedback spring rod of the armature assembly was eliminated in the double-redundancy electro-hydraulic servo valve (DREHSV), which employed a redundant design in contrast to the typical double-nozzle flapper electro-hydraulic servo valve (DNFEHSV). The pilot stage was mainly composed of four torque motors, and the double-system spool was adopted in the power stage. Consequently, the difficulty of spool displacement control was increased. By artificially changing the structural parameters of the simulation model in accordance with the theoretical analysis through AMESim, this paper aimed to study the dynamics and static characteristics of the DREHSV. The advantage of redundant design was further demonstrated by disconnecting working coils and setting the different worn parts of the spool. On the test bench, the necessary experiments were performed. Through simulation, it was discovered that when the clogged degree of the nozzle is increased, the zero bias value increases, the pressure and flow gain remain unchanged, and the internal leakage decreases. The pressure gain changes very little, the flow gain close to the zero position grows, the zero leakage increases significantly, and the pilot stage leakage changes very little as a result of the wear of the spool throttling edge. The basic consistency between the simulation curves and the experimental findings serve to validate the accuracy of the AMESim model. The findings can serve as a theoretical guide for the design, debugging, and maintenance of the DREHSV. The simulation model is also capable of producing a large amount of sample data for DREHSV fault diagnosis using a neural network.

ObjectiveAutism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD.MethodsIn this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits.ResultsThe TL of the ASD group was shorter than the TD group (p

The curing stage is of great importance in flavor formation during Chinese bacon processing. Ultrasound-assisted curing plays an essential role in the Lipid oxidation of meat products. In this study, GC–MS and electronic nose were used to analyze the influence of different power ultrasonic-assisted curing on the flavor formation of Chinese bacon. Through the analysis of phospholipid and lipase, the fundamental precursors of ultrasonic on the flavor of Chinese bacon were determined. It was found that there were differences in the flavor contour description of Chinese bacon between the ultrasonic treatment group, mainly due to the change in the W1W sensor. A total of 28 volatile compounds were detected by GC–MS, and the aldehyde content increased with ultrasonic power. PC and PE are the main flavor precursors in the curing process. This study provides a theoretical basis for improving the curing technology of Chinese bacon.