Levonorgestrel protected Au10 cluster for hypochlorite sensing in living organisms.

BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.

Gossypium arboreum PPD2 facilitates root architecture development to increase plant resilience to salt stress.

The jasmonic acid (JA) signaling pathway plays an important role in plant responses to abiotic stresses. The PEAPOD (PPD) and jasmonate ZIM-domain (JAZ) protein in the JA signaling pathway belong to the same family, but their functions in regulating plant defense against salt stress remain to be elucidated. Here, Gossypium arboreum PPD2 was overexpressed in Arabidopsis thaliana and systematically silenced in cotton for exploring its function in regulating plant defense to salt stress. The GaPPD2-overexpressed Arabidopsis thaliana plants significantly increased the tolerance to salt stress compared to the wild type in both medium and soil, while the GaPPD2-silenced cotton plants showed higher sensitivity to salt stress than the control in pots. The antioxidant activities experiment showed that GaPPD2 may mitigate the accumulation of reactive oxygen species by promoting superoxide dismutase accumulation, consequently improving plant resilience to salt stress. Through the exogenous application of MeJA (methy jasmonate) and the protein degradation inhibitor MG132, it was found that GaPPD2 functions in plant defense against salt stress and is involved in the JA signaling pathway. The RNA-seq analysis of GaPPD2-overexpressed A. thaliana plants and receptor materials showed that the differentially expressed genes were mainly enriched in antioxidant activity, peroxidase activity, and plant hormone signaling pathways. qRT-PCR results demonstrated that GaPPD2 might positively regulate plant defense by inhibiting GH3.2/3.10/3.12 expression and activating JAZ7/8 expression. The findings highlight the potential of GaPPD2 as a JA signaling component gene for improving the cotton plant resistance to salt stress and provide insights into the mechanisms underlying plant responses to environmental stresses.

Cotton HD-Zip I transcription factor GhHB4-like regulates the plant response to salt stress.

Soil salinity is a major environmental constraint to plant production. The homeodomain-leucine zipper I (HD-Zip I) transcription factors play a crucial role in growth, development and defence responses of plants. However, the function and underlying mechanism of HD-Zip I in cotton remain unexplored. This study investigated the role of GhHB4-like, a cotton HD-Zip I gene, in plant tolerance to salt stress. Ectopic expression of GhHB4-like gene enhanced, while its silencing impaired the salt tolerance in Arabidopsis. Y1H and effector-reporter assays revealed that GhHB4-like activated the expression of GhNAC007, which is essential for salt resistance. Knock-down of GhNAC007 also impaired salt resistance of cotton plants. In addition, GhHB4-like-GhNAC007 might have positively regulated the expression of GhMYB96 and ABA signalling-related genes, thereby leading to enhanced salt resistance. Interestingly, deleting motifs 3 and 5 near the 3'-end of GhHB4-like significantly enhanced GhNAC007 activation, indicating that both motifs acted as transcriptional activation inhibitory domains. The results suggest that GhHB4-like-GhNAC007 regulated plant response to salt stress, potentially by modulating GhMYB96 and ABA signalling-related genes.

A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.

[Clinical application of endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants].

Objective: To investigate the effectiveness of endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. Methods: The clinical data of 138 female patients with breast cancer who met the selection criteria between April 2019 and December 2023 were retrospectively analyzed. The mean age of the patients was 43.8 years (range, 27-61 years). The maximum diameter of the tumors ranged from 1.00 to 7.10 cm, with an average of 2.70 cm. Pathological examination showed that 108 cases were positive for both estrogen receptor and progesterone receptor, and 40 cases were positive for human epidermal growth factor receptor 2. All patients underwent endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants. The operation time, intraoperative blood loss, prosthesis size, and occurences of nipple-areola complex (NAC) ischemia, flap ischemia, infection, and capsular contracture were recorded. The Breast-Q2.0 score was used to evaluate breast aesthetics, patient satisfaction, and quality of life (including the social mental health score, breast satisfaction score, and chest pain score). Patients were divided into two groups based on the time of operation after the technique was implemented: group A (within 1 year, 25 cases) and group B (after 1 year, 113 cases). The above outcome indicators were compared between the two groups. Furthermore, based on the postoperative follow-up duration, patients were classified into a short-term group (follow-up time was less than 1 year) and a long-term group (follow-up time was more than 1 year). The baseline data and postoperative Breast-Q2.0 scores were compared between the two groups. Results: The average operation time was 120.76 minutes, the average intraoperative blood loss was 23.77 mL, and the average prosthesis size was 218.37 mL. Postoperative NAC ischemia occurred in 21 cases (15.22%), flap ischemia in 30 cases (21.74%), infection in 23 cases (16.67%), capsular contracture in 33 cases (23.91%), and prosthesis removal in 2 cases (1.45%). The operation time of group A was significantly longer than that of group B ( P<0.05), and there was no significant difference in intraoperative blood loss, prosthesis size, and related complications between the two groups ( P>0.05). All patients were followed up 3-48 months (mean, 20 months). There were 33 cases in the short-term group and 105 cases in the long-term group. There was no significant difference in baseline data such as age, body mass index, number of menopause cases, number of neoadjuvant chemotherapy cases, number of axillary lymph node dissection cases, breast cup size, degree of breast ptosis, and postoperative radiotherapy constituent ratio between the two groups ( P>0.05). At last follow-up, the breast satisfaction score in the patients' Breast-Q2.0 score ranged from 33 to 100, with an average of 60.9; the social mental health score ranged from 38 to 100, with an average of 71.3; the chest pain score ranged from 20 to 80, with an average of 47.3. The social mental health score of the long-term group was significantly higher than that of the short-term group ( P<0.05); there was no significant difference in breast satisfaction scores and chest pain scores between the two groups ( P>0.05). No patient died during the follow-up, and 2 patients relapsed at 649 days and 689 days postoperatively, respectively. The recurrence-free survival rate was 98.62%. Conclusion: Endoscopic radical mastectomy for breast cancer combined with total pectoral muscle reconstruction with breast implants has fewer complications and less damage, and the aesthetic effect of reconstructed breast is better.

Research progress in the ethnopharmacology, phytochemistry, pharmacology, toxicology, and quality control of Valeriana jatamansi Jones.

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.

A constrained maximum likelihood approach to developing well-calibrated models for predicting binary outcomes.

The added value of candidate predictors for risk modeling is routinely evaluated by comparing the performance of models with or without including candidate predictors. Such comparison is most meaningful when the estimated risk by the two models are both unbiased in the target population. Very often data for candidate predictors are sourced from nonrepresentative convenience samples. Updating the base model using the study data without acknowledging the discrepancy between the underlying distribution of the study data and that in the target population can lead to biased risk estimates and therefore an unfair evaluation of candidate predictors. To address this issue assuming access to a well-calibrated base model, we propose a semiparametric method for model fitting that enforces good calibration. The central idea is to calibrate the fitted model against the base model by enforcing suitable constraints in maximizing the likelihood function. This approach enables unbiased assessment of model improvement offered by candidate predictors without requiring a representative sample from the target population, thus overcoming a significant practical challenge. We study theoretical properties for model parameter estimates, and demonstrate improvement in model calibration via extensive simulation studies. Finally, we apply the proposed method to data extracted from Penn Medicine Biobank to inform the added value of breast density for breast cancer risk assessment in the Caucasian woman population.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

Scrutinizing a Lactococcus lactis mutant with enhanced capacity for extracellular electron transfer reveals a unique role for a novel type-II NADH dehydrogenase.

Lactococcus lactis, a lactic acid bacterium used in food fermentations and commonly found in the human gut, is known to possess a fermentative metabolism. L. lactis, however, has been demonstrated to transfer metabolically generated electrons to external electron acceptors, a process termed extracellular electron transfer (EET). Here, we investigated an L. lactis mutant with an unusually high capacity for EET that was obtained in an adaptive laboratory evolution (ALE) experiment. First, we investigated how global gene expression had changed, and found that amino acid metabolism and nucleotide metabolism had been affected significantly. One of the most significantly upregulated genes encoded the NADH dehydrogenase NoxB. We found that this upregulation was due to a mutation in the promoter region of NoxB, which abolished carbon catabolite repression. A unique role of NoxB in EET could be attributed and it was directly verified, for the first time, that NoxB could support respiration in L. lactis. NoxB, was shown to be a novel type-II NADH dehydrogenase that is widely distributed among gut microorganisms. This work expands our understanding of EET in Gram-positive electroactive microorganisms and the special significance of a novel type-II NADH dehydrogenase in EET.IMPORTANCEElectroactive microorganisms with extracellular electron transfer (EET) ability play important roles in biotechnology and ecosystems. To date, there have been many investigations aiming at elucidating the mechanisms behind EET, and determining the relevance of EET for microorganisms in different niches. However, how EET can be enhanced and harnessed for biotechnological applications has been less explored. Here, we compare the transcriptomes of an EET-enhanced L. lactis mutant with its parent and elucidate the underlying reason for its superior performance. We find that one of the most significantly upregulated genes is the gene encoding the NADH dehydrogenase NoxB, and that upregulation is due to a mutation in the catabolite-responsive element that abolishes carbon catabolite repression. We demonstrate that NoxB has a special role in EET, and furthermore show that it supports respiration to oxygen, which has never been done previously. In addition, a search reveals that this novel NoxB-type NADH dehydrogenase is widely distributed among gut microorganisms.

Assisted reproductive technologies and postpartum depressive symptoms: A meta-analysis.

BACKGROUND: Assisted reproductive technologies (ARTs) have become the main treatment for infertility. ART treatment can be a stressful life event for infertile females. Whether there is an association between ARTs and postpartum depressive symptoms (PDS) has not been established. METHODS: PubMed, MEDLINE, EMBASE, PsycINFO, and CNKI were searched. The pooled outcome was the difference in incidence of PDS within 1 year postpartum between ARTs and the spontaneous pregnancy group. RESULTS: A total of 12 cohort studies, which were conducted in eight developed countries and two developing countries, were involved. In total, 106,338 pregnant women, including 4990 infertile females with ARTs treatment and 101,348 women with spontaneous pregnancy, were enrolled in our final analysis. ARTs women had a lower incidence of PDS compared to the spontaneous pregnancy group according to a random effect model (OR = 0.83, 95 % CI: 0.71-0.97, p = 0.022, I2 = 62.0 %). Subgroup analyses indicated that studies on late PDS (follow-up: 3-12 months postpartum) were more heterogeneous than those on early PDS (follow-up: <3 months postpartum) (I2 = 24.3 % vs. I2 = 0 %, interaction p-value < 0.001). There was a strong relationship between ARTs and late PDS (OR = 0.65, 95 % CI: 0.55-0.77, p < 0.001). Therefore, the possible source of heterogeneity was the postpartum evaluation time, which was confirmed by post-hoc meta-regression. LIMITATIONS: Some underlying confounders, such as previous psychiatric illness, the limited availability of ARTs, and ethnic disparities, cannot be ignored and may have biased interpretation of the results. CONCLUSION: The available data suggested that ARTs were associated with lower incidence of PDS, especially when follow-up lasted over 3 months. However, these findings should be interpreted with caution. Better-designed trials are needed to confirm this association.

Risk factors and prediction score for new-onset diabetes mellitus after liver transplantation.

AIM: New-onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new-onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks. METHODS: We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database. RESULTS: A total of 468 patients met the outlined criteria and finished the follow-up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724-0.846) in the experimental population and 0.782 (95% CI: 0.708-0.856) in the validation population. CONCLUSIONS: Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.

[Retracted] Reduced miR­202 levels enhanced oral cancer development via targeting Sp1.

[This retracts the article DOI: 10.3892/etm.2019.7603.].

iJAZ-based approach to engineer lepidopteran pest resistance in multiple crop species.

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway.

BACKGROUND: Periodontitis is a chronic inflammatory disease resulting from bacterial plaque infection. While the involvement of activating transcription factor 1 (ATF1) has been extensively explored in various human diseases, its specific role in periodontitis remains unclear. This study aims to elucidate the expression and biological function of ATF1 in the context of periodontitis. METHODS: Primary human periodontal ligament cells (hPDLCs) were procured from clinical samples and subsequently characterized. Following treatment with P. gingivalis lipopolysaccharide (LPS, 10 µg/mL), hPDLCs underwent transfection with either ATF1 vector or siRNA. The expression levels of ATF1 in LPS-treated hPDLCs or transfected cells were evaluated through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß), were quantified using Enzyme-linked Immunosorbent Assay (ELISA). The assessment of osteogenic proteins, such as runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG), as well as noncanonical nuclear factor-kappaB (NF-κB) pathway-related proteins (p65, p-p65, IkBα, p-IkBα), was conducted using western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry assays were employed to detect cell viability. RESULTS: LPS induced an inflammatory response and hindered the osteogenic differentiation of hPDLCs (p < 0.05, p < 0.01). Furthermore, ATF1 silencing enhanced cell proliferation and suppressed apoptosis in LPS-stimulated hPDLCs (p < 0.05, p < 0.01). ATF1 silencing not only restrained the inflammatory response but also promoted the osteogenic differentiation of LPS-stimulated hPDLCs (p < 0.05, p < 0.01). Importantly, ATF1 silencing effectively blocked the LPS-induced activation of the NF-κB signaling pathway (p < 0.05, p < 0.01, p < 0.001). CONCLUSIONS: ATF1 emerges as a promising treatment option, inhibiting the osteogenic differentiation of hPDLCs and mitigating the inflammatory response by preventing the phosphorylation of the NF-κB signaling pathway.

Outpatient cervical ripening with balloon catheters: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: One in four labors are induced. The process of cervical ripening can be lengthy and pre-labor hospitalization is required. Outpatient cervical ripening can be an attractive alternative. OBJECTIVES: To evaluate the efficacy and safety of outpatient cervical ripening with a balloon catheter compared with inpatient balloon catheter or prostaglandin E2 (PGE2). SEARCH STRATEGY: The PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases were searched from their inception to October 15, 2022. SELECTION CRITERIA: Randomized controlled trials comparing the outpatient balloon catheter with inpatient balloon catheter or inpatient PGE2 for term cervical ripening. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis was performed. The primary outcome was the cesarean delivery rate. The secondary outcomes included instrumental delivery, the time from intervention-to-birth, oxytocin augmentation, total hospital duration, and maternal/neonatal adverse events. MAIN RESULTS: Twenty-nine randomized controlled trials with a total of 6004 participants were identified. No difference in the cesarean delivery rate was revealed among the three interventions. Compared with inpatient balloon catheter, outpatient balloon catheter had shorter total hospital duration (mean difference -8.58, 95% confidence interval -17.02 to -1.10). No differences were revealed in the time from intervention-to-birth, instrumental delivery, postpartum hemorrhage, 5-min Apgar score less than 7, umbilical cord arterial pH less than 7.1, and neonatal intensive care unit admission among the three interventions. CONCLUSIONS: Outpatient balloon catheter in low-risk term pregnancies is an available option that could be considered for cervical ripening. The safety and effectiveness are comparable to inpatient cervical ripening methods.

Relief of Residual Stress in Bulk Thermosets in the Glassy State by Local Bond Exchange.

The covalently cross-linked network gives thermosets superior thermal, mechanical, and electrical properties, which, however, squarely makes the large residual stress that is inevitably induced during preparation hardly relieved in the glassy state. In this work, an incredible reduction in residual stress is successfully achieved in bulk thermosets in the glassy state through introducing highly dynamic thiocarbamate bonds by "click" reactions of thiols and isocyanates. Due to the excellent dynamic behaviors of thiocarbamate bonds, local network rearrangement is achieved through thermal stimulation, while the strong 3D cross-linked network is well maintained. Ultimately, a decrease by 44% in residual stress is detected by simply annealing samples at 30 °C below glass transition temperature (Tg), during which they could well maintain more than 98.4% of the storage modulus. After the annealing, more uniform residual stress distribution is also observed, showing a 32% decline in sample standard deviation. However, the residual stress of epoxy resin, a typical thermoset as a reference, changes little even after annealing at Tg. The results prove it a feasible strategy to reduce residual stress in bulk thermosets in the glassy state by introducing proper dynamic covalent bonds.

Quantitative Risk Assessment of Salmonella in Breaded Pork Products in China.

Pork products were the most common media of Salmonella in China, breaded pork products as a very popular meat presently, whose Salmonella risk should be drawn to attention. Given that quantitative risk assessment is a more scientific method for risk evaluation, a quantitative risk assessment model of Salmonella in breaded pork products was first constructed from processing to consumption, and was used for assessing the risk and the effective interventions in this study. The data of Salmonella contamination in breaded pork products during processing were obtained from the actual detection data of samples from a representative meat processing plant. With combining the predictive microbial modeling and dose-response relationship, the risk of Salmonella in breaded pork products was charactered, and the probability of Salmonella infection per meal was found to be 5.585 × 10-9. Based on the results of sensitivity analysis, the curing and seasoning process was found to be the key control point for Salmonella contamination during the processing, and consumer behavior was the key control point affecting the probability of Salmonella infection from processing to consumption. The model was also applied for assessing the effectiveness of risk interventions, and among the nine interventions given, control of thawing temperature before cooking such as microwave thawing could reduce the risk of infection by 30.969-fold, while cooking the products thoroughly, Salmonella would not pose a pathogenic hazard to consumers. The model and the assessed results in this study may provide guidance on microbial control in producing process and safety consumption of breaded pork products.

Saikosaponin a activates tet1/dll3/notch1 signalling and promotes hippocampal neurogenesis to improve depression-like behavior in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri, also named "Chaihu" in Chinese, is a substance derived from the dry roots of Bupleurum chinense DC. [Apiaceae] and Bupleurum scorzonerifolium Willd. [Apiaceae]. Radix Bupleuri was initially recorded as a medicinal herb in Shen Nong Ben Cao Jing, the earliest monograph concerning traditional Chinese medicine (TCM). Ever since, Radix Bupleuri has been broadly used to alleviate exterior syndrome, disperse heat, modulate the liver-qi, and elevate yang-qi in TCM. Radix Bupleuri has also been utilized as an important component in Xiaoyaosan, a classical formula for relieving depression, which was originated from the famous Chinese medical book called "Tai Ping Hui Min He Ji Ju Fang" in Song Dynasty. Currently, many valuable pharmacological effects of Radix Bupleuri have been explored, such as antidepressant, neuroprotective activities, antiinflammation, anticancer, immunoregulation, etc. Former studies have illustrated that Saikosaponin A (SSa), one of the primary active components of Radix Bupleuri, possesses potential antidepressant properties. However, the underlying mechanisms still remain unknown. AIM OF THE STUDY: We used a chronic social defeat stress (CSDS) mouse model to explore the ameliorative effects and potential mechanisms of SSa in depressive disorder in vivo. MATERIALS AND METHODS: The CSDS mouse model was established and mice underwent behavioral studies using assays such as the social interaction test (SIT), sucrose preference test (SPT), forced-swim test (FST), tail suspension test (TST), and open field test (OFT). Western blotting, immunofluorescence, and Golgi staining were performed to investigate signaling pathway activity, and alterations in synaptic spines in the hippocampus. To model the anticipated interaction between SSa and Tet1, molecular docking and microscale thermophoresis (MST) techniques were employed. Finally, sh-RNA Tet1 was employed for validation via lentiviral transfection in CSDS mice to confirm the requirement of Tet1 for SSA efficacy. RESULTS: SSa dramatically reduced depressed symptoms, boosted the expression of Tet1, Notch, DLL3, and BDNF, encouraged hippocampus development, and enhanced the dendritic spine density of hippocampal neurons. In contrast, Tet1 knockdown in CSDS mice dampened the beneficial effects of SSa on depressive symptoms. CONCLUSIONS: Therefore, our results suggest that SSa significantly activates the Tet1/Notch/DLL3 signaling pathways and promotes hippocampal neurogenesis to exert antidepressant effects in the CSDS mouse model in vivo. The present results also provide new insight into the importance of the Tet1/DLL3/Notch pathways as potential targets for novel antidepressant development.

Value of salivary gland imaging based on deep learning and Delta radiomics in evaluation of salivary gland injury following 131I therapy post thyroid cancer surgery / 中华核医学与分子影像杂志

Objective:To explore the value of salivary gland imaging based on deep learning and Delta radiomics in assessing salivary gland injury after 131I treatment in post-thyroidectomy thyroid cancer patients. Methods:A retrospective analysis on 223 patients (46 males, 177 females, age(47.7±14.0) years ) with papillary thyroid cancer, who underwent total thyroidectomy and 131I treatment in Affiliated Hospital of Guilin Medical University between December 2019 and January 2022, was conducted. All patients underwent salivary gland 99Tc mO 4- imaging before and after 131I therapy. The patients were categorized according to salivary gland function based on 99Tc mO 4- imaging results (normal salivary gland vs salivary gland injury), and divided into training and test sets in a ratio of 7∶3. A ResNet-34 neural network model was trained using images at the time of maximum salivary gland radioactivity and those based on background radioactivity counts for structured image feature data. The Delta radiomics approach was then used to subtract the image feature values of the two periods, followed by feature selection through t-test, correlation analysis, and the least absolute shrinkage and selection operator( LASSO) algorithm, to develop logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) predictive models. The diagnostic performance of 3 models for salivary gland function on the test set was compared with that of the manual interpretation. The AUCs of the 3 models on the test set were compared (Delong test). Results:Among the 67 cases of the test set, the diagnostic accuracy of 3 physicians were 89.6%(60/67), 83.6%(56/67), and 82.1%(55/67) respectively, with the time required for diagnosis of 56, 74 and 55 min, respectively. The accuracies of LR, SVM, and KNN models were 91.0%(61/67), 86.6%(58/67), and 82.1%(55/67), with the required times of 12.5, 15.3 and 17.9 s, respectively. All 3 radiomics models demonstrated good classification and predictive capabilities, with AUC values for the training set of 0.972, 0.965, and 0.943, and for the test set of 0.954, 0.913, and 0.791, respectively. There were no significant differences among the AUC values for the test set ( z values: 0.72, 1.18, 1.82, all P>0.05). Conclusion:The models based on deep learning and Delta radiomics possess high predictive value in assessing salivary gland injury following 131I treatment after surgery in patients with thyroid cancer.

Association of Fine Particulate Matter Constituents with the Predicted 10-Year Atherosclerotic Cardiovascular Disease Risk: Evidence from a Large-Scale Cross-Sectional Study.

Little is known concerning the associations of fine particulate matter (PM2.5) and its constituents with atherosclerotic cardiovascular disease (ASCVD). A total of 31,162 participants enrolled from the Henan Rural Cohort were used to specify associations of PM2.5 and its constituents with ASCVD. Hybrid machine learning was utilized to estimate the 3-year average concentration of PM2.5 and its constituents (black carbon [BC], nitrate [NO3-], ammonium [NH4+], inorganic sulfate [SO42-], organic matter [OM], and soil particles [SOIL]). Constituent concentration, proportion, and residual models were utilized to examine the associations of PM2.5 constituents with 10-year ASCVD risk and to identify the most hazardous constituent. The isochronous substitution model (ISM) was employed to analyze the substitution effect between PM2.5 constituents. We found that each 1 µg/m3 increase in PM2.5, BC, NH4+, NO3-, OM, SO42-, and SOIL was associated with a 3.5%, 49.3%, 19.4%, 10.5%, 21.4%, 14%, and 28.5% higher 10-year ASCVD risk, respectively (all p < 0.05). Comparable results were observed in proportion and residual models. The ISM found that replacing BC with other constituents will generate the greatest health benefits. The results indicated that long-term exposure to PM2.5 and its constituents were associated with increased risks of ASCVD, with BC being the most attributable constituent.