Low complexity sub-baud rate sampling reception in a bandwidth-limited IM/DD system.

This Letter presents what is to our knowledge a novel approach to reduce the digital signal processing (DSP) complexity in intensity modulation and direct detection (IM/DD) systems, which is critical for short-reach optical communication systems with severe bandwidth limitations. We propose a sub-baud rate sampling reception method utilizing a polyphase feedforward equalizer-based maximum likelihood sequence estimation (PFFE-MLSE), which could operate effectively under a sampling rate of 0.6 samples per symbol. This new architecture eliminates the need for resampling, allowing the adaptive equalizer to operate with significantly reduced complexity-over 60% compared to traditional FFE-MLSE. An offline experiment, transmitting a 100-Gbaud on-off keying (OOK) signal over a 5-km single-mode fiber (SMF) link, demonstrates the feasibility of our approach with bit error ratio (BER) meeting the KP4-forward error correction (KP4-FEC) threshold in the optical back-to-back (OBTB) scenario and 7% hard-decision FEC (HD-FEC) threshold in the 5-km SMF transmission.

Highly Dispersive Gold Nanoclusters Confined within Micropores of Defective UiO-66 for Highly Efficient Aldehyde Oxidation at Mild Conditions.

The oxidative esterification of aldehydes under mild conditions remains a significant challenge. This study introduces a unique defective UiO-66 to achieve gold nanoclusters (AuNCs) for efficient aldehyde oxidation under mild conditions. The construction and characterization of these materials are thoroughly investigated by techniques of XRD, SEM and TEM images, FT-IR, Raman, and XPS spectrum, emphasizing the unique microporous in defective UiO-66 are conducive to the fabrication of AuNCs. The catalytic performance of the prepared materials in aldehyde oxidation reactions is systematically evaluated, demonstrating the remarkable efficiency of dispersed Au@UiO-66-25 with high-content (9.09 wt%) Au-loading and ultra-small size (~2.7 nm). Moreover, mechanistic insights into the catalytic process under mild conditions (70 °C for 1 h) are provided, elucidating the determination of defective UiO-66 in the confined fabrication of AuNCs and subsequent furfural adsorption, which underlie the principles governing the observed enhancements. This study establishes the groundwork for the synthesis of highly dispersed and catalytically active metal nanoparticles using defective MOFs as a platform, advancing the catalytic esterification reaction of furfural to the next level.

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1ß, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.

Intramedullary nail fixation assisted by locking plate for complex subtrochanteric femur fractures: A retrospective study.

BACKGROUND: This study aims to compare therapeutic effects of two methods in complicated subtrochanteric femur fractures surgery: intramedullary nail fixation assisted with lateral monocortical locking plate versus intramedullary nail fixation assisted with supplementary cables. METHODS: From June 2015 to June 2020, seventy-seven patients with complex subtrochanteric fractures (i.e., Seinsheimer's classification type IV or V) were included in this study. Thirty-six patients (plate group) were operated using the intramedullary nail fixation assisted by lateral monocortical locking plate, and forty-one patients (cable group) were using the intramedullary nail fixation assisted by cables. The clinical information and demographic results were collected and compared. RESULTS: Operation time of plate group was shorter than cable group and the Incisions length of plate group was longer. The fluoroscopy times were 22.8 ± 8.2 in plate group and 33.0 ± 9.0 in cable group (p < 0.01). Compared with the cable group, patients in plate group used less cerclage cables (p < 0.01). Patients in the plate group has less medial cortex displacement compared with the cable group. (p = 0.038). As for the angular difference of neck shaft angle between operated hip and uninjured hip, plate group has less difference compared with the cable group. Time to union was 14.2 ± 3.1 weeks in plate group which is shorter than the cable group (17.9 ± 4.8 weeks). In terms of follow up period, number of malunion, Harris hip score, walking ability and traumatic hip rating scale, no significant differences were detected. CONCLUSIONS: Our results suggest that using lateral monocortical plate as an auxiliary way may have a longer surgical incision and more intraoperative blood loss, however, the operation time is shorter, the fluoroscopy times is less, and the time to union is shorter. Intramedullary nail fixation assisted by lateral monocortical locking plate may be a new option for patients with complex subtrochanteric femur fractures.

Lithium chloride inhibits infectious bronchitis virus-induced apoptosis and inflammation.

Avian infectious bronchitis (IB) was caused by infectious bronchitis virus (IBV), a coronavirus, which leads to enormous economic losses in the poultry industry. Studies have shown that lithium chloride (LiCl) is a good virus inhibitor. Through cell culture, virus infection, and RT-qPCR, we found that LiCl could down-regulate the apoptosis-related genes Caspase-3 and Bax, up-regulate Bcl-2, and down-regulate the inflammatory-related genes (NF-κB, NLRP3, TNF-α, and IL-1ß) via inhibiting virus replication. Finally, clinical trials showed that LiCl could inhibit IBV-induced apoptosis and inflammatory in chicken embryos as well as reduce the mortality and deformity rate of chicken embryos. The results showed that LiCl has antiviral activity against IBV and clinical effects. Further studies are required to explore the exact action mechanism of LiCl on IBV-induced apoptosis and inflammation.

ATP5B promotes the metastasis and growth of gastric cancer by activating the FAK/AKT/MMP2 pathway.

Adenosine triphosphate (ATP) in the tumor microenvironment serves a vital role during tumor progression. ATP synthase F1 ß subunit (ATP5B) is one of the most important subunits of ATP synthase and increases cellular ATP levels. ATP5B reportedly participates in carcinogenesis in several tumors. However, the regulatory mechanisms of ATP5B remain poorly understood in gastric cancer (GC). Here, we determined that high ATP5B expression in tumor tissues of GC is positively correlated with age, the tumor size, the TNM stage, lymph node metastasis, and patients' poor prognosis. The overexpression of ATP5B in GC cells elevated the cellular ATP content and promoted migration, invasion and proliferation. The levels of MMP2 expression, phosphorylated FAK, and phosphorylated AKT were increased after ATP5B overexpression in GC cells. Additionally, ATP5B overexpression increased the extracellular ATP level through the secretion of intracellular ATP and activated the FAK/AKT/MMP2 signaling pathway. ATP5B-induced downstream pathway activation was induced through the plasma membrane P2X7 receptor. Inhibitors of P2X7, FAK, AKT, and MMP2 suppressed the proliferative, migratory, and invasive capabilities of GC cells. In conclusion, our experiments indicate that ATP5B contributes to tumor progression of GC via FAK/AKT/MMP2 pathway. ATP5B, therefore, may be a biomarker of poor prognosis and a potential therapeutic target for GC.

Controlling the Morphology and Titanium Coordination States of TS-1 Zeolites by Crystal Growth Modifier.

Developing an effective strategy to synthesize perfect titanosilicate TS-1 zeolite crystals with desirable morphologies, enriched isolated framework Ti species, and thus enhanced catalytic oxidation properties is a pervasive challenge in zeolite crystal engineering. We here used an amino acid l-carnitine as a crystal growth modifier and ethanol as a cosolvent to regulate the morphologies and the Ti coordination states of TS-1 zeolites. During the hydrothermal crystallization process, the introduced l-carnitine can not only tailor the anisotropic growth rates of zeolite crystals but also induce the formation of uniformly distributed framework Ti species through building a suitable chemical interaction with the Ti precursor species. Condition optimizations could afford the generation of perfect hexagonal plate TS-1 crystals and elongated platelet TS-1 crystals enriched in tetrahedral framework Ti sites (TiO4) or mononuclear octahedrally coordinated Ti species (TiO6). Both samples showed significant improvement in catalytic activity for the H2O2-mediated epoxidation of alkenes. In particular, the elongated platelet TS-1 enriched in "TiO6" species afforded the highest activity in 1-hexene epoxidation, with a turnover frequency (TOF) of up to 131 h-1, which is approximately twice as high as that of the conventional TS-1 zeolite (TOF: 65 h-1) and even higher than those of the literature-reported TiO6-containting TS-1 catalysts derived from the hydrothermal post-treatment of TS-1 zeolites. This work demonstrates that the morphologies and the titanium coordination states of TS-1 zeolites can be effectively tuned by directly introducing suitable crystal growth modifiers, thus providing new opportunities for developing highly efficient titanosilicate zeolite catalysts for important catalytic applications.

Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer.

BACKGROUND: Increasing evidence indicates that angiogenesis plays an important role in tumor progression. The function of cathepsin L (CTSL), an endosomal proteolytic enzyme, in promoting tumor metastasis is well recognized. The mechanisms by which CTSL has promoted the angiogenesis of gastric cancer (GC), however, remains unclear. METHODS: The nuclear expression levels of CTSL were assessed in GC samples. The effects of CTSL on GC angiogenesis were determined by endothelial tube formation analysis, HUVEC migration assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the CDP/Cux/VEGF-D pathway was analyzed by angiogenesis antibody array, Western blot, co-immunoprecipitation (Co-IP) and dual-luciferase reporter assay. RESULTS: In this study, we found that the nuclear CTSL expression level in GC was significantly higher than that in adjacent nontumor gastric tissues and was a potential important clinical prognostic factor. Loss- and gain-of-function assays indicated that CTSL promotes the tubular formation and migration of HUVEC cells in vitro. The CAM assay also showed that CTSL promotes angiogenesis of GC in vivo. Mechanistic analysis demonstrated that CTSL can proteolytically process CDP/Cux and produce the physiologically relevant p110 isoform, which stably binds to VEGF-D and promotes the transcription of VEGF-D, thus contributing to the angiogenesis of GC. CONCLUSION: The findings of the present study suggested that CTSL plays a constructive role in the regulation of angiogenesis in human GC and could be a potential therapeutic target for GC.

Oncostatin M receptor, positively regulated by SP1, promotes gastric cancer growth and metastasis upon treatment with Oncostatin M.

BACKGROUND: Oncostatin M receptor (OSMR) is a member of the interleukin 6 (IL-6) receptor family that transduces signaling events of Oncostatin M (OSM). OSM-OSMR signaling plays a key role in inflammation and cancer progression. However, the role of OSM-OSMR in gastric cancer (GC) is still unknown. METHODS: OSMR expression in GC was determined by real-time PCR (RT-PCR), immunohistochemistry (IHC) and Western blot. The effects of OSM-OSMR on GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo were examined. The pathways underlying OSM-OSMR signaling were explored by Western blot. Regulatory mechanism between SP1 and OSMR was explored in vitro. RESULTS: OSMR was highly expressed in GC tissues and its expression level was closely associated with age, T stage, Lauren classification, lymph node metastasis, TNM stage and worse prognosis of patients with GC. Knockdown of OSMR expression in GC cells significantly inhibited cell proliferation, migration, invasion, and EMT in vitro, as well as tumorigenesis and peritoneal metastasis in vivo induced by OSM. These effects mediated by OSM-OSMR were dependent on the activation of STAT3/FAK/Src signaling. SP1 could bind to the promoter region of human OSMR gene from - 255 to - 246 bp, and transcriptionally regulated OSMR overexpression in GC cells. CONCLUSIONS: OSM-OSMR contributes to GC progression through activating STAT3/FAK/Src signaling, and OSMR is transcriptionally activated by SP1.

The change of albumen quality during the laying cycle and its potential physiological and molecular basis of laying hens.

To elucidate the regulatory mechanisms that impact variability in albumen quality of laying hens from the peak of lay to the late production phase. A 60-wk study was conducted on a cohort of 20,000 Hy-Line Brown laying hens from 20 to 80 wk old. Before commencement at 20 wk, the 10-wk-old hens were acclimatized for 10 wk. This study examined changes in albumen quality, serum, and liver antioxidant capacity, magnum morphology, and expression of albumen-protein-related genes in the magnum. To reduce sampling error, we collected eggs (n = 90) from pre-determined cages at every sampling point (5-wk intervals), and 8 hens were selected at 10-wk intervals for blood and tissue collection. Our findings revealed that age significantly affected most evaluated parameters. Albumen gel properties, including hardness, gumminess, and chewiness, increased significantly with age (P < 0.05). With the increasing of hens' age from 20 to 80 wk, the albumen proportion of eggs was decreased, but eggshell proportion, yolk proportion, thick albumen proportion, thick to thin ratio, thick albumen solid content, albumen height, Haugh units (HU), and yolk color were increased and then decreased (P < 0.05). Compared to hens aged 20 to 60 wk, the hens (70-80 wk) had significantly reduced total antioxidant capacity (TAC) and glutathione levels (GSH) in the liver and lower serum TAC and superoxide dismutase levels (SOD) (P < 0.05). The magnum mucosal folds were highest in 40 to 60 wk-old hens, and the luminal diameter increased with age (P < 0.05). In the magnum, the mRNA expression levels for OVA, CPE, and NUP205 increased significantly between 30 and 40 wk, while FBN1 expression was higher between 30 and 50 wk (P < 0.05). At 70 to 80 wk, the expression of BRCA2 was significantly downregulated (P < 0.05). Albumen height, thick albumen proportion with protein secretion-related genes, enhanced antioxidant function, and luminal diameter correlated positively. However, the thick-to-thin albumen ratio negatively correlated with BRCA2, downregulated in aged laying hens. We used principal component and cluster analysis to deduce albumen quality changes during 3 phases: 25 to 35, 40 to 55, and 60 to 80 wk. The decline in albumen quality in aging hens is linked with decreased antioxidant capacity, magnum health, and downregulation of key genes involved in protein synthesis and secretion. These findings emphasize critical albumen quality changes in laying hens and suggest molecular pathways underlying age-related albumen quality alterations.

Effect of Genistein and Glycitein on production performance, egg quality, antioxidant function, reproductive hormones and related-genes in pre-peak laying hens.

Genistein (GEN) and Glycitein (GLY), are types of isoflavone extracted mainly from soy plants, although GEN is associated with stronger antioxidant and growth-promoting effects. The impact of dietary GEN and GLY on reproductive performance, egg quality, and bone quality were investigated in the study. Additionally, to explore the underlying mechanism of action, the serum hormone levels and reproductive-related genes were investigated. A total of 378 Hy-Line Brown laying hens (120 days old) were randomly allocated to 3 dietary groups (Control), (GLY, and GEN at 50 mg/kg respectively) for a period of 8 wk. Each treatment has 126 birds (7 replicates of 18 birds each). Results were analyzed in 2 phases: wk 1 to 4, and 5 to 8 of feeding trial. The results indicated that supplemental GEN significantly increased egg number, hen-day production (HDP), and egg mass during wk 1 to 4, whereas, both glycitein and genistein increased egg number, egg weight, egg mass, HDP and improved feed-egg-ratio during wk 5 to 8. Egg quality analysis revealed significant improvements in eggshell quality; gloss, thickness, strength, and albumen quality indices (albumen height, Haugh unit, thick albumen fraction) due to dietary treatments. Also, the tibia strength, Ca content in the tibia ash and bone mineral content, were significantly increased by the dietary treatments. Significant increases in the serum levels of E2, LH, FSH, T3, T4, and GH, and the activity of antioxidant enzymes; SOD, CAT, GSH while reducing the level of MDA, was notable with the treatments. Additionally, reproductive-related genes: ESR1, FSHR, PRLR, GNRH1 were significantly upregulated by the supplementation of GEN and GLY. The efficacy of GEN in relation to the evaluated parameters was superior to that of GLY. Conclusively, we speculate that the improvement on laying performance, egg quality and tibia quality may be related to promoting effect of isoflavones on calcium metabolism, antioxidant function, reproductive hormones and related genes. Therefore, supplemental GEN at a dosage level of 50 mg/kg, can be used to promote laying performance, sustain egg production and maintain the physiological function of young laying hens.

Associations between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus: A prospective cohort study from NHANES 2007-2018.

AIMS: To investigate the dose-response association between physical activity and all-cause and cardiovascular mortality in adults with type 2 diabetes mellitus and the effects of replacing sedentary behavior with physical activity. METHODS: 4808 adults with type 2 diabetes mellitus were included in NHANES 2007-2018. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. Isotemporal substitution analyses were further to determine the possible benefit of replacing sedentary time. RESULTS: During a median follow-up of 6.58 years, 902 deaths occurred, including 290 deaths from cardiovascular disease. Compared with the inactive group, the low-active and high-active groups were associated with declined risks of all-cause mortality [HRs (95% CIs) 0.64 (0.50, 0.83); 0.60 (0.50, 0.73), respectively] and cardiovascular mortality [0.50 (0.29, 0.88); 0.54 (0.39, 0.76)), respectively]. Dose-response analysis showed a significant U-shaped curve between physical activity and all-cause and cardiovascular mortality. Replacing 30 min/day of sedentary time with physical activity was substantially linked to a reduced risk of 8-32% mortality. CONCLUSION: A high level of PA of 40.52 and 31.66 MET-h/week was respectively related to the lowest risk of all-cause and cardiovascular mortality. Replacing sedentary time with physical activity could benefit the type 2 diabetes mellitus population.

Histological and molecular difference in albumen quality between post-adolescent hens and aged hens.

The decline in albumen quality resulting from aging hens poses a threat to the financial benefits of the egg industry. Exploring the underlying mechanisms from the perspective of cell molecules of albumen formation is significant for the efficient regulation of albumen quality. Two individual groups of Hy-Line Brown layers with ages of 40 (W40) and 100 (W100) wk old were used in the present study. Each group contained over 2,000 birds. This study assessed the egg quality, biochemical indicators and physiological status of hens between W40 and W100. Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in magnum tissues between W40 and W100. In the W40 group, significant increases (P < 0.05) were notable for albumen quality (thick albumen solid content, albumen height, Haugh unit), serum indices (calcium, estrogen, and progesterone levels), magnum histomorphology (myosin light-chain kinase content, secretory capacity, mucosal fold, goblet cell count and proportion) as well as the total antioxidant capacity of the liver. However, the luminal diameter of the magnum, albumen gel properties and random coil of the albumen were increased (P < 0.05) in the W100 group. The activity of glutathione, superoxidase dismutase, and malondialdehyde in the liver, magnum, and serum did not vary (P > 0.05) among the groups. Proteomic analysis revealed the identification of 118 differentially expressed proteins between the groups, which comprised proteins associated with protein secretion, DNA damage and repair, cell proliferation, growth, antioxidants, and apoptosis. Furthermore, Kyoto Encyclopedia of Genes pathway analysis revealed that BRCA2 and FBN1 were significantly downregulated in Fanconi anemia (FA) and TGF-ß signaling pathways in W100, validated through quantitative real-time PCR (qRT-PCR). In conclusion, significant age-related variations in albumen quality, and magnum morphology are regulated by proteins involved in antioxidant capacity.

Effects of Dietary Rare Earth Chitosan Chelate on Performance, Egg Quality, Immune and Antioxidant Capacity, and Intestinal Digestive Enzyme Activity of Laying Hens.

Rare earth chitosan chelate salt (RECC) is a potential feed additive and is a product of the chelation effect between rare earth ions and chitosan. This research study aims to explore the effects of dietary RECC on performance, egg quality, intestinal digestive function, and the immune and antioxidant capacity of laying hens in the late phase of production. A total of 360 56-week-old Dawu Jinfeng laying hens were randomly allotted into four treatment groups with six replicates per treatment and 15 birds per replicate. The laying hens were fed the basal diet supplemented with, respectively, 0 (control: CON), 100 (R1), 200 (R2), and 400 (R3) mg/kg for 8 weeks. Dietary RECC significantly improved average daily feed intake (ADFI) and average daily egg yield in both linear and quadratic manner (p < 0.05). In addition, albumen height and HU were improved significantly (p < 0.05) in a dose-dependent manner of RECC. In addition, a significant decrease (p < 0.05) in serum TP, IgA, and MDA for the R1 group and IgG in the R2 group were notable, while the increase in serum TP and decrease in T-AOC were found for R3 dietary group compared to CON (p < 0.05). The level of intestinal IL-2 and TNF-α was decreased by dietary RECC (p < 0.01). The activities of the digestive enzyme (α-Amylase, lipase, and Trypsin) showed a quadratic change with an increase and then decrease in response to increasing dose of RECC, 200 mg/kg RECC significantly increased the activity of lipase and Trypsin (p < 0.01). Supplementation of dietary RECC at low doses compared to higher doses impacted positive effects on the antioxidant capacity and immune function (p < 0.05). The utilization of RECC as a feed additive in the diet of aged laying hens exerted beneficial effects on egg production, albumen quality, humoral immunity, inflammatory response, and activity of digestive enzymes. Thus, the regulation of antioxidant capacity and duodenal function via increased enzyme activity and immune and inflammatory response were critical to the improvement of laying performance and egg quality in aged hens. The optimal supplemental dose is 100-200 mg/kg.

Glycosylated proteins with abnormal glycosylation changes are potential biomarkers for early diagnosis of breast cancer.

Conventional cancer management relies on tumor type and stage for diagnosis and treatment, which leads to recurrence and metastasis and death in young women. Early detection of proteins in the serum aids diagnosis, progression, and clinical outcomes, possibly improving survival rate of breast cancer patients. In this review, we provided an insight into the influence of aberrant glycosylation on breast cancer development and progression. Examined literatures revealed that mechanisms underlying glycosylation moieties alteration could enhance early detection, monitoring, and therapeutic efficacy in breast cancer patients. This would serve as a guide for the development of new serum biomarkers with higher sensitivity and specificity, providing possible serological biomarkers for breast cancer diagnosis, progression, and treatment.

ZnO/Cu2O heterojunction integrated fiber-optic biosensor for remote detection of cysteine.

Indium tin oxide, semiconductor nanomaterial ZnO, and Cu2O were first loaded on the surface of the optical fiber to form an optical fiber probe. Large-volume macroscopic spatial light is replaced by an optical fiber path, and remote light injection is implemented. Based on the optical fiber probe, a photoelectrochemical biosensor was constructed and remote detection of cysteine was realized. In this tiny device, the optical fiber probe not only acts as a working electrode to react with the analyte but also directs the light exactly where it is needed. Simultaneously, the electrochemical behavior of cysteine on the surface of the working electrode is dominated by diffusion-control, which provides strong support for quantitative detection. Then, under the bias potential of 0 V, the linear range of the fiber-optic-based cysteine biosensor was 0.01∼1 µM, the regression coefficient (R2) value was 0.9943. In spiked synthetic urine, the detection of cysteine was also realized by the integrated biosensor. Moreover, benefiting from the low optical fiber loss, the new structure also possesses a unique remote detection function. This work confirms that photoelectrochemical biosensors can be integrated via optical fibers and retain comparable sensing performance. Based on this property, different materials can also be loaded on the surface of the optical fiber for remote detection of other analytes. It is expected to facilitate the research on fiber-optic-based integrated biosensors and show application prospects in diverse fields such as biochemical analysis and disease diagnosis.

Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation.

BACKGROUND: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects. METHODS: The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial. RESULTS: We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1ß). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos. CONCLUSIONS: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.

Calponin 1 increases cancer-associated fibroblasts-mediated matrix stiffness to promote chemoresistance in gastric cancer.

The mechanical microenvironment regulated by cancer-associated fibroblasts (CAFs) influence tumor progression. Chemotherapeutic interventions including 5-Fluorouracil (5-Fu) are commonly used for primary treatment of patients with advanced gastric cancer (GC), and the development of acquired resistance to 5-Fu limits the clinical efficacy of these chemotherapies. However, if and how the interplay between CAFs and the mechanical microenvironment regulates GC response to 5-Fu is poorly understood. In this study, we demonstrate that high-level expression of calponin 1(CNN1) in gastric CAFs predicts poor clinical outcomes of GC patients, especially for those treated with 5-Fu. CNN1 knockdown in CAFs improves the effectiveness of 5-Fu in reducing tumor growth in a mouse GC model and confers increased sensitivity to 5-Fu in a 3D culture system. Furthermore, CNN1 knockdown impairs CAF contraction and reduces matrix stiffness without affecting the expression of matrix proteins. Mechanistically, CNN1 interacts with PDZ and LIM Domain 7 (PDLIM7) and prevents its degradation by the E3 ubiquitin ligase NEDD4-1, which leads to activation of the ROCK1/MLC pathway. The increased matrix stiffness, in turn, contributes to 5-Fu resistance in GC cells by activating YAP. Taken together, our data reveal a critical role of the mechanical microenvironment in 5-Fu resistance, which is modulated by CNN1hi CAFs-mediated matrix stiffening, indicating that targeting CAFs may provide a novel option for overcoming drug resistance in GC.

Regulation of bone health through physical exercise: Mechanisms and types.

Osteoporosis, characterized by bone mineral density reduction, bone mass loss, increased bone fragility, and propensity to fractures, is a common disease in older individuals and one of the most serious health problems worldwide. The imbalance between osteoblasts and osteoclasts results in the predominance of bone resorption and decreased bone formation. In recent years, it has been found that regular and proper exercise not only helps prevent the occurrence of osteoporosis but also adds benefits to osteoporosis therapy; accordingly, bone homeostasis is closely associated with mechanical stress and the intricate crosstalk between osteoblasts and osteoclasts. In this review, we summarize the mechanisms of exercise on osteoporosis and provide new proposals for the prevention and treatment of osteoporosis.

Prognostic characteristics of immune subtypes associated with acute myeloid leukemia and their identification in cell subsets based on single-cell sequencing analysis.

Immune genes play an important role in the development and progression of acute myeloid leukemia (AML). However, the role of immune genes in the prognosis and microenvironment of AML remains unclear. In this study, we analyzed 151 AML patients in the TCGA database for relevant immune cell infiltration. AML patients were divided into high and low immune cell infiltration clusters based on ssGSEA results. Immune-related pathways, AML pathways and glucose metabolism pathways were enriched in the high immune cell infiltration cluster. Then we screened the differential immune genes between the two immune cell infiltration clusters. Nine prognostic immune genes were finally identified in the train set by LASSO-Cox regression. We constructed a model in the train set based on the nine prognostic immune genes and validated the predictive capability in the test set. The areas under the ROC curve of the train set and the test set for ROC at 1, 3, 5 years were 0.807, 0.813, 0.815, and 0.731, 0.745, 0.830, respectively. The areas under ROC curve of external validation set in 1, 3, and 5 years were 0.564, 0.619, and 0.614, respectively. People with high risk scores accompanied by high TMB had been detected with the worst prognosis. Single-cell sequencing analysis revealed the expression of prognostic genes in AML cell subsets and pseudo-time analysis described the differentiation trajectory of cell subsets. In conclusion, our results reveal the characteristics of immune microenvironment and cell subsets of AML, while it still needs to be confirmed in larger samples studies. The prognosis model constructed with nine key immune genes can provide a new method to assess the prognosis of AML patients.