Controlled Preparation of Highly Stretchable, Crack-Free Wrinkled Surfaces with Tunable Wetting and Optical Properties.

Constructing wrinkles by utilizing strain-driven surface instability in film-substrate systems is a general method to prepare micronano structures, which have a wide range of applications in smart surfaces and devices such as flexible electronics, reversible wetting, friction, and optics. However, cracks generated during the preparation and use process significantly affect the uniformity of wrinkled surfaces and degrade the functional properties of the film devices. The realization of crack-free wrinkles with high stretchability in hard film systems is still a great challenge. Here, we report on a facile technique for controllable preparation of large-area, highly stretchable, crack-free wrinkled surfaces by ultraviolet ozone (UVO) treatment of Ecoflex. The thickness dependence of the wrinkles and the in situ wrinkling process during mechanical loading are investigated. The wrinkles including striped, labyrinth-like, herringbone, and transitional structures are controllable by changing strain mode (uniaxial or biaxial), loading history (simultaneous or sequential), strain anisotropy, and gradient loading. The wrinkled surfaces obtained using UVO-treated Ecoflex have tunable wetting and optical properties and can maintain excellent mechanical stability under large strains. This study provides a facile method for the preparation of large-area, crack-free wrinkles, which is simple, fast, low-cost, and robust. The resulting wrinkled surfaces remain stable under high stretching, which is beneficial for many practical applications, especially in the cases of large strains.

Impact of Infection-Related Immunosuppressant Reduction on Kidney Transplant Outcomes: A Retrospective Study Considering the Temporal Dynamics of Immunosuppressive Requirements.

Immunosuppressant reduction (ISR) is a common treatment for kidney transplant recipients experiencing infections, but its impacts on kidney transplant outcomes remains unclear. This retrospective single-center study included 300 patients who underwent kidney transplantation between January 2017 and April 2020. The post-transplant timeline was divided into four distinct phases: ≤1 month, 2-6 months, 7-12 months, and >12 months. Patients were categorized based on the presence of clinically relevant infections and whether they received ISR. Significant differences were observed in the spectrum of clinically relevant infections across the post-transplant phases. During the ≤1 month phase, primary infections were associated surgical operation, such as urinary tract infections involving Enterococcus spp. and Candida spp. Cytomegalovirus and BK polyomavirus (BKPyV) infections increased during the 2-6 months and 7-12 months periods. Approximately one-third of patients experienced ISR due to infection, with BKPyV infections being the primary causes. Recipients who experienced their first ISR due to infection between 2-6 months and 7-12 months had worse graft survival comparing with patients without any infections. ISR due to infections between 2 and 6 months was associated with a higher risk of rejection. Tailored ISR strategies should be developed according to temporal dynamics of immunosuppressive intensity to prevent rejection.

Resistance characterization of the natural population and resistance mechanism to pyraclostrobin in Lasiodiplodia theobromae.

Lasiodiplodia theobromae is the main pathogen of mango stem-end rot disease, causing mango fruit decay and major economic loss. QoI resistance has been found in field populations of L. theobromae. The characterization and resistance mechanism of pyraclostrobin-resistant L. theobromae was investigated by using a combination of bioassays and biochemical and molecular methods. The pyraclostrobin resistance among the L. theobromae population samples from Hainan was 93.41%. The resistant isolates were stable after successive subculturing for 10 times on PDA. Cross-resistance was observed only between the Qols pyraclostrobin and azoxystrobin. The alternative oxidase (AOX) inhibitor SHAM notably decreased the EC50 values of pyraclostrobin for all tested L. theobromae isolates. Induction of AOX by pyraclostrobin was observed in mycelia cells of L. theobromae. After treatment with pyraclostrobin, the final ATP and AOX contents of all sensitive isolates were significantly lower than those of resistant isolates. The relevant mutation and high expression of the cytochrome b gene were not detected in resistant isolates. However, there were 4 mutations in the AOX gene, which were only observed in highly resistant isolates. Pretreatment with pyraclostrobin resulted in a significant upregulation of AOX gene expression, and the average expression level of the highly resistant isolates was 33-fold that of the control group. These results suggested that the AOX pathway is responsible for resistance to pyraclostrobin, and that the AOX-related resistance mechanism is common in field populations of L. theobromae in Hainan mango orchards.

Clinical characteristics of patients with listeriosis. / æŽæ–¯ç‰¹èŒç— æ‚£è€ çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To investigate the clinical characteristics of patients with listeriosis and to provide a basis for diagnosis, treatment, prevention and control of hospital infection. METHODS: A total of 10 inpatients, who suffered from the listeriosis in Xiangya Hospital, Central South University from January 2013 to June 2019, were retrospectively collected for this study. The characteristics of the patients' age, gander, basic information, case type, clinical manifestations, first consultation department, days of diagnosis, infection indicator, specimen type, results of drug sensitivity, treatment plan, hospital infection or not, outcome, follow-up data were analyzed. RESULTS: Two cases were pregnant women and other were non-pregnant adults among 10 patients with listeriosis. Among them, there were 3 cases with hospital acquired infection. The age of patient onset was 27-71 years old, and the time from onset to diagnosis was 5-36 days. Five cases had fever, and other 5 cases had not fever. There were headache, fatigue, local pain, and other specialized symptoms in the 10 patients.The white blood cell count,the neutrophil ratio, the inflammatory index C-reactive protein, the procalcitonin were all increased, and the erythrocyte sedimentation was accelerated in the 10 patients.All the patients were sensitive to ampicillin, penicillin G, meropenem, and compound sinomine. CONCLUSIONS: Listeriosis often affects the patients with low immunity, which often leads to misdiagnosis or missed diagnosis in clinic.So early prevention, early diagnosis, and early treatment can reduce mortality; it is important for departments of nosocomial infection management to manage patients' diet for avoiding outbreaks of listeriosis in hospital.

Risk factors for urinary tract infection in kidney transplantation from brain death donor and its role in graft function. / è„‘æ­»äº¡å™¨å®˜æçŒ®è‚¾ç§»æ¤æœ¯åŽå‘ç”Ÿå°¿è·¯æ„ŸæŸ“çš„å±é™©å› ç´ åŠå ¶å¯¹ç§»æ¤è‚¾åŠŸèƒ½çš„å½±å“.

OBJECTIVES: Urinary tract infection (UTI) is the most common infection complication after kidney transplantation, and the reports of the incidence vary greatly among different centers. This study aims to explore the risk factors for UTI after kidney transplantation with the donation from brain death (DBD) and the impact on graft function, thus to provide theoretical basis for comprehensive prevention and treatment of UTI after kidney transplantation. METHODS: The clinical and laboratory data of DBD kidney transplantation from January 2017 to December 2018 in Xiangya Hospital, Central South University were collected and retrospectively analyzed. Patients were assigned into an UTI group and a non-UTI group. The base line characteristics, post-transplant complications, and graft function were compared between the 2 groups. Multivariate logistic regression was used to analyze the risk factors for UTI. RESULTS: A total of 212 DBD kidney transplant recipients were enrolled in this study. UTI occurred in 44 (20.75%) patients after transplantation. The female, the time of indwelling catheter, and postoperative urinary fistula were independent risk factors for UTI after DBD kidney transplantation. A total of 19 strains of gram-positive bacteria, 12 strains of gram-negative bacteria , and 10 strains of fungi were isolated from the urine of 44 UTI patients. The UTI after kidney transplantation significantly increased time of hospital stay (P<0.001) and raised the cost for antibiotics (P=0.004). The graft function was much worse in the UTI group compared with the non-UTI group (P<0.001) at 3 months after transplantation. Twenty (45.45%) patients recurred UTI within one year after transplantation. Non-hemodialysis before transplantation and perioperative combination of antibacterial and antifungal drugs were independent risk factors for recurrence of UTI. CONCLUSIONS: UTI after DBD kidney transplantation transplantation affects the renal function at 3 months and increases the patient's economic burden.

Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer.

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-ß, ß-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.

Involvement of glutathione peroxidases in the occurrence and development of breast cancers.

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers' attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.

Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function.

The ability of liver to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis. Autophagy encompasses mechanisms of cell survival, including capturing, degrading, and recycling of intracellular proteins and organelles in lysosomes. During negative nutrient status, autophagy provides substrates to sustain cellular metabolism and hence, tissue function. Severe negative energy balance in dairy cows is associated with fatty liver. The aim of this study was to investigate the hepatic autophagy status in dairy cows with severe fatty liver and to determine associations with biomarkers of liver function and inflammation. Liver and blood samples were collected from multiparous cows diagnosed as clinically healthy (n = 15) or with severe fatty liver (n = 15) at 3 to 9 d in milk. Liver tissue was biopsied by needle puncture, and serum samples were collected on 3 consecutive days via jugular venipuncture. Concentrations of free fatty acids and ß-hydroxybutyrate were greater in cows with severe fatty liver. Milk production, dry matter intake, and concentration of glucose were all lower in cows with severe fatty liver. Activities of serum aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase, and γ-glutamyl transferase were all greater in cows with severe fatty liver. Serum concentrations of haptoglobin and serum amyloid A were also markedly greater in cows with severe fatty liver. The mRNA expression of autophagosome formation-related gene ULK1 was lower in the liver of dairy cows with severe fatty liver. However, the expression of other autophagosome formation-related genes, beclin 1 (BECN1), phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), autophagy-related gene (ATG) 3, ATG5, and ATG12, did not differ. More important, ubiquitinated proteins, protein expression of sequestosome-1 (SQSTM1, also called p62), and microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3)-II was greater in cows with severe fatty liver. Transmission electron microscopy revealed an increased number of autophagosomes in the liver of dairy cows with severe fatty liver. Taken together, these results indicate that excessive lipid infiltration of the liver impairs autophagic activity that may lead to cellular damage and inflammation.

Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild fatty liver.

The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To determine the effects of palmitic acids (PA), one of the major component of fatty acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were isolated from healthy calves and treated with various concentrations of PA (0, 50, 100, and 200 µM). Dairy cows with mild fatty liver displayed hepatic lipid accumulation. The protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα) and mRNA levels of acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), acyl-CoA oxidase (ACO), and carnitine palmitoyltransferase 1A (CPT1A) were significantly higher in dairy cows with mild fatty liver than in control cows. The hepatic mitochondrial DNA content, mRNA levels of oxidative phosphorylation complexes I to V (CO 1-V), protein levels of cytochrome c oxidase subunit IV (COX IV), voltage dependent anion channel 1 (VDAC1), peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), and adenosine triphosphate (ATP) content were all markedly increased in the liver of dairy cows with mild fatty liver compared with healthy cows. The PA treatment significantly increased lipid accumulation; protein levels of SREBP-1c and PPARα; and mRNA levels of ACC1, FAS, ACO, and CPT1A in calf hepatocytes. Moreover, the mitochondrial DNA content, mRNA levels of CO 1-V, protein levels of COX IV, VDAC1, PGC-1α, NRF1, mitochondrial transcription factor A, and ATP content were significantly increased in PA-treated hepatocytes compared with control hepatocytes. The protein level of mitofusin-2 was significantly decreased in PA-treated groups. In conclusion, lipid synthesis and oxidation, number of mitochondria, and ATP production were increased in the liver of dairy cows with mild fatty liver and PA-treated calf hepatocytes. These changes in hepatic mitochondria and lipid metabolism may be the adaptive mechanism of dairy cows with mild fatty liver.

Alzheimer's disease diagnostic accuracy by fluid and neuroimaging ATN framework.

OBJECTIVES: The ATN's different modalities (fluids and neuroimaging) for each of the Aß (A), tau (T), and neurodegeneration (N) elements are used for the biological diagnosis of Alzheimer's disease (AD). We aim to identify which ATN category achieves the highest potential for diagnosis and predictive accuracy of longitudinal cognitive decline. METHODS: Based on the availability of plasma ATN biomarkers (plasma-derived Aß42/40 , p-tau181, NFL, respectively), CSF ATN biomarkers (CSF-derived Aß42 /Aß40 , p-tau181, NFL), and neuroimaging ATN biomarkers (18F-florbetapir (FBP) amyloid-PET, 18F-flortaucipir (FTP) tau-PET, and fluorodeoxyglucose (FDG)-PET), a total of 2340 participants were selected from ADNI. RESULTS: Our data analysis indicates that the area under curves (AUCs) of CSF-A, neuroimaging-T, and neuroimaging-N were ranked the top three ATN candidates for accurate diagnosis of AD. Moreover, neuroimaging ATN biomarkers display the best predictive ability for longitudinal cognitive decline among the three categories. To note, neuroimaging-T correlates well with cognitive performances in a negative correlation manner. Meanwhile, participants in the "N" element positive group, especially the CSF-N positive group, experience the fastest cognitive decline compared with other groups defined by ATN biomarkers. In addition, the voxel-wise analysis showed that CSF-A related to tau accumulation and FDG-PET indexes more strongly in subjects with MCI stage. According to our analysis of the data, the best three ATN candidates for a precise diagnosis of AD are CSF-A, neuroimaging-T, and neuroimaging-N. CONCLUSIONS: Collectively, our findings suggest that plasma, CSF, and neuroimaging biomarkers differ considerably within the ATN framework; the most accurate target biomarkers for diagnosing AD were the CSF-A, neuroimaging-T, and neuroimaging-N within each ATN modality. Moreover, neuroimaging-T and CSF-N both show excellent ability in the prediction of cognitive decline in two different dimensions.

A novel Gaussian sum quaternion constrained cubature Kalman filter algorithm for GNSS/SINS integrated attitude determination and positioning system.

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).

Clinical efficacy of the bared external anal sphincter (BEAS) in high horseshoe-shaped anal fistulas: Protocol for a real-world, prospective cohort study.

Background: High horseshoe-shaped anal fistula (HHAF) is a complex disease that manifests in the perianal region and typically requires surgical intervention for treatment. However, the current therapeutic approaches are limited by the high rates of postoperative recurrence and anal incontinence. To overcome the limitations of traditional surgical approaches, we introduce the bared external anal sphincter (BEAS) technique. Our study aims to compare the clinical efficacy of BEAS surgery with that of the modified Hanley procedure in a real-world setting. Materials and methods: This single-centre, prospective cohort study will be conducted in a tertiary hospital in China and aims to evaluate the short-term clinical efficacy and safety of BEAS surgery and modified Hanley surgery in HHAF patients from March 2024 to March 2026. Data from the prospective database of this tertiary referral hospital will be used to obtain insights into the clinical outcomes of these surgical treatments. The primary outcome of this study will be the wound healing rate within six months, while the secondary outcomes will include the time to return to work, the maximum visual analogue scale pain score (VAS-PS) within 1-5 days postsurgery, and the Cleveland Clinic Florida Incontinence Score (CCF-IS) and Quality of Life in Anal Fistula Questionnaire Score (QoLAF-QS) at 1, 3, and 6 months postsurgery. Moreover, logistic regression analysis will be used to explore the risk factors for anal fistula recurrence after the BEAS procedure. Discussion: This will be the first cohort study to evaluate the differences in therapeutic outcomes between patients who undergo BEAS surgery and patients who undergo surgery via the modified Hanley procedure. By conducting a detailed observation of the efficacy and treatment results of these two surgical methods, this study aims to reveal the differences the clinical effectiveness of these approaches and to provide evidence-based support for future randomized controlled trials (RCTs).

Synergistic effect of cannabidiol with dasatinib on lung cancer by SRC/PI3K/AKT signal pathway.

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson's disease.

Backgrounds: Numerous lines of evidence support the intricate interplay between Parkinson's disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls. Methods: A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls. Results: PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores. Conclusion: These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.

MiR-338-5p, a novel metastasis-related miRNA, inhibits triple-negative breast cancer progression by targeting the ETS1/NOTCH1 axis.

Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.

A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer.

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats.

Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined. METHODS: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 106 cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κß ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, ß-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting. RESULTS: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, ß-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. CONCLUSION: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/ß-catenin pathway and inhibition of inflammation.

Brassinosteroids control male fertility by regulating the expression of key genes involved in Arabidopsis anther and pollen development.

The development of anther and pollen is important for male reproduction, and this process is coordinately regulated by many external and internal cues. In this study, we systematically examined the male reproductive phenotypes of a series of brassinosteroid biosynthetic and signaling mutants and found that, besides the expected cell-expansion defects, these mutants also showed reduced pollen number, viability, and release efficiency. These defects were related with abnormal tapetum and microspore development. Using both real-time quantitative RT-PCR and microarray experiments, we found that the expression of many key genes required for anther and pollen development was suppressed in these mutants. ChIP analysis demonstrated that BES1, an important transcription factor for brassinosteroid signaling, could directly bind to the promoter regions of genes encoding transcription factors essential for anther and pollen development, SPL/NZZ, TDF1, AMS, MS1, and MS2. Taken together, these data lead us to propose that brassinosteroids control male fertility at least in part via directly regulating key genes for anther and pollen development in Arabidopsis. Our work provides a unique mechanism to explain how a phytohormone regulates an essential genetic program for plant development.

Examining the impact of early enteral nutritional support on postoperative recovery in patients undergoing surgical treatment for gastrointestinal neoplasms.

BACKGROUND: Patients with gastrointestinal tumors often suffer from poor nutritional status during treatment. Surgery is the main treatment for these patients, but the long postoperative recovery period is often accompanied by digestive and absorption dysfunction, leading to further deterioration of the nutritional status. Early enteral nutrition support is hypothesized to be helpful in improving this situation, but the exact effects have yet to be studied in depth. AIM: To observe the effect of early enteral nutritional support on postoperative recovery in patients with surgically treated gastrointestinal tract tumors, with the expectation that by improving the nutritional status of patients, the recovery process would be accelerated and the incidence of complications would be reduced, thus improving the quality of life. METHODS: A retrospective analysis of 121 patients with gastrointestinal tract tumors treated in our hospital from January 2020 to January 2023 was performed. Fifty-three of these patients received complete parenteral nutrition support as the control group for this study. The other 68 patients received early enteral nutritional support as the observation group of this study. The clinical indicators comparing the two groups included time to fever, time to recovery of postoperative bowel function, time to postoperative exhaustion, and length of hospital stay. The changes in immune function and nutritional indexes in the two groups were compared. Furthermore, we utilized the SF-36 scale to compare the changes in the quality of life between the two groups of patients. Finally, the occurrence of postoperative complications between the two patient groups was also compared. RESULTS: The postoperative fever time, postoperative bowel function recovery time, postoperative exhaustion time, and hospitalization time were all higher in the control group than in the observation group (P < 0.05). The levels of CD3+, CD4+, immunoglobulin (Ig) A, IgM, and IgG in the observation group were significantly higher than those in the control group at 1 d and 7 d postoperatively, while CD8+ was lower than in the control group (P < 0.05). Total protein, albumin, prealbumin, and transferrin levels were significantly higher in the observation group than in the control group at 7 d postoperatively (P < 0.05). The SF-36 scores of patients in the observation group were significantly higher than those in the control group (P < 0.0001). The overall incidence of adverse reactions after the intervention was significantly lower in the control group than in the observation group (P = 0.021). CONCLUSION: We found that patients with gastrointestinal tumors are nutritionally vulnerable, and early enteral nutrition support programs can improve the nutritional status of patients and speed up postoperative recovery. This program can not only improve the immune function of the patient and protect the intestinal function, but it can also help to improve the quality of life of the patient. However, this program will increase the incidence of complications in patients. Caution should be taken when adopting early enteral nutrition support measures for patients with gastric cancer. The patient's condition and physical condition should be comprehensively evaluated and closely monitored to prevent possible complications.

Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC. Firstly, we found that the mRNA expression of Notch1 and CD73 in cisplatin-treated patient material associated with poor clinical outcome. Further, both were upregulated at the protein level in cisplatin-resistant TNBC cell lines. Overexpression of Notch1 intracellular domain (termed N1ICD) increased expression of CD73, whereas knockdown of Notch1 decreased CD73 expression. Using chromatin immunoprecipitation and Dual-Luciferase assay it was identified that N1ICD directly bound the CD73 promoter and activated transcription. Taken together, these findings suggest CD73 as a direct downstream target of Notch1, providing an additional layer to the mechanisms underlying Notch1-mediated cisplatin resistance in TNBC.