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This study investigates the relationship between Employee-Centred Corporate Social Responsibility (ECCSR) and organisational resilience, focusing on empirically validating the mediating effects through rigorous model comparison approach to enhance the robustness of the findings. Non-probability approach, specifically purposive sampling was employed to reach the targeted respondents. Respondents were selected based on two criteria: being full-time employees and having been employed during and after the global pandemic. Data were gathered through a self-administered questionnaire and analysed using variance-based structural equation modeling (SEM). The results indicate a significant positive effect of ECCSR on organisational resilience. Additionally, the mediation effects of workplace well-being and social well-being are confirmed through a model comparison approach, which quantifies the level of uncertainty introduced by these mediating effects. The study is novel in three aspects: First, it categorises employee wellbeing into two dimensions, namely, workplace well-being and social well-being; second, it conceptualises the impetus of ECCSR in terms of the Matthew Effect, highlighting the self-reinforcing nature of benefit accumulation; and third, it employs a quality assessment to quantify the presence of mediators. Organisations are encouraged to consider and leverage the positive impacts associated with ECCSR, such as increased employee engagement and retention, as well as improved corporate reputation.

Muscle is one of the important quality of fish. However, there is still a lack of sufficient understanding of the mechanism of muscle growth regulation in fish. In this study, the expression patterns of 10 reported muscle development related genes are analyzed in zebrafish during growth or under water flow stress. Myogenic regulatory factors (MyoD, MyoG, MRF4), myostatin regulatory genes (Mstna, Mstnb) and myoblast development-related genes (Pax7, Prmt5, Desmin, MYHC) are significantly increased expression at somite stage and muscle effect stage embryos in zebrafish. The mRNA levels of the muscle development related genes are up-regulated in 7-day fries and 30-day juvenile of zebrafish. And there are differences in the expression levels of seven muscle development related genes (MyoD, Myf5, MyoG, Mstna, Mstnb, Desmin, MYHC) between the large and small individuals of 20-day-old zebrafish. Results indicated that short-term water flow stressing can promote zebrafish muscle growth, while prolonged water flow stress may lead to motor fatigue and affect growth in zebrafish. This research provides a foundation for further exploration of the growth regulation mechanism in fish, and is helpful on fish farming.

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

The adoption of multi-channel strategies by retailers, encompassing both online and offline modalities, has fundamentally transformed consumer shopping behaviors, resulting in a significant increase in mobile shopping. Nonetheless, the long-term success of mobile shopping apps is heavily dependent on consumers’ continuous use. Regrettably, the existing studies on this area remain vague and require further exploration. This study aims to close this gap by examining Malaysian consumers’ continuance intention and continuance use of mobile shopping through the lens of ISSM in the context of mobile shopping apps. We utilised a quantitative approach and successfully collected 369 responses from Klang Valley, using purposive sampling techniques. The predictive hypotheses developed were validated using Partial Least Square – Structural Equation Modelling (PLS-SEM) and were further supplemented with Necessary Condition Analysis (NCA) to determine must-have factors based on necessary logic. The PLS-SEM results confirmed the association between continuance intention and continuance use. The findings revealed that service quality and system quality are associated with satisfaction, but not information quality. Additionally, service quality, system quality, and information quality, together with satisfaction, trust and incentive have a positive significant influence on Malaysians’ mobile shopping app continuance intention. However, the NCA results indicated that system quality is the sole must-have factor that contributes to satisfaction. Meanwhile, service quality, system quality, information quality, satisfaction, trust, and incentive are the must-have predictors for mobile shopping app continuance intention. The study sheds light on previously unexplored aspects namely, continuance intention and continuance use, within the framework of the ISSM in the context of mobile shopping. By doing so, it offers more refined and actionable insights to improve consumer experience and foster sustained engagement with mobile shopping apps. Simultaneously, it contributes to the advancement of knowledge regarding the foundational constructs and their interconnectedness, thereby enhancing theoretical development in this domain.

Abstract Background Ultrasonography (US) still has some limitations in the differentiation of benign and malignant breast masses. Therefore, we introduced new technologies such as S-Detect, microvascular flow imaging (MVFI), and strain elastography (SE) into the examination and compared the multimodal method with Breast Imaging Reporting and Data System (BI-RADS). Objectives This prospective study aimed to evaluate the value of multimodal diagnostic methods that add S-Detect, MFI, and SR to US in differentiating benign from malignant breast masses. Methods We recruited 186 patients with 189 masses between July 2021 and March 2022. The masses were examined using US, S-Detect, SR, and MFI before biopsy, and the benign and malignant differentiation value of each and their combination were assessed compared with surgical pathology results using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Subgroup analysis by lesion size was also performed. Results The respective optimal cutoff values of SR and MFI for differentiating benign from malignant masses were 3.15 and 2.45, respectively, and the sensitivity and specificity were 79.3% and 85.6% and 94.6% and 69.1%, respectively. The multimodal AUC (0.907), sensitivity (97.8%), accuracy (90.5%), PPV (84.9%), and NPV (97.6%) were larger than those of each modality (p

Abstract Background We aimed to evaluate the added value of inversion imaging in differentiating between benign and malignant breast masses when combined with the Breast Imaging Reporting and Data System (BI-RADS). Methods A total of 364 patients with 367 breast masses (151 benign and 216 malignant) who underwent conventional ultrasound and inversion imaging prior to breast surgery were included. A 5-point inversion score (IS) scale was proposed based on the masses’ internal echogenicity and distribution characteristics in the inversion images. The combination of IS and BI-RADS was compared with BI-RADS alone to evaluate the value of inversion imaging for breast mass diagnosis. The diagnostic performance of the BI-RADS and its combination with IS for breast masses were analyzed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results The IS for malignant breast masses (3.96 ± 0.77) was significantly higher than benign masses (2.58 ± 0.98) (P

Alzheimer’s disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly understood. In this study, we investigated the effects of treadmill exercise on the exercise ability of APP/PS1 transgenic AD mice and explored potential gene expression changes in their skeletal muscle. The APP/PS1 mice were subjected to a treadmill exercise for 12 weeks, followed by the Morris water maze and the open field test. After behavioral experiments, the changes in morphology, area, collagen fiber deposition, and ultrastructure of the skeletal muscle were determined; the balance of skeletal muscle protein synthesis and decomposition was analyzed; and changes in gene expression were investigated using RNA-Seq. We found that this exercise strategy can promote the learning and memory abilities of AD mice, reduce their anxiety-like behavior, improve their exercise ability, alleviate skeletal muscle atrophy, and optimize the microstructure. It can also enhance skeletal muscle protein synthesis and decomposition and improve several signaling pathways, such as the JAK–STAT, Wnt, and NOD-like receptors while decreasing calcium, cAMP, cGMP–PKG, and other signaling pathways. Six KEGG enrichment signaling pathways were downregulated and five signaling pathways were upregulated in the AD mice compared with wild-type mice, and these pathways were precisely reversed after the treadmill exercise. The expression of transcription factors such as Fosb and Egr1 in the skeletal muscle of AD mice decreased, followed by a decrease in the regulated target genes Socs1, Srrm4, and Il1b, a trend that was reversed following the exercise intervention. After exercise, AD mice exhibited a similar gene expression to that of wild-type mice, indicating enhanced exercise ability. The potential regulatory pathways and related genes identified in this study provide valuable insights for the clinical management and treatment of AD.

The occurrence of type 2 diabetes mellitus (T2DM), a worldwide chronic disease, is mainly caused by insufficient insulin production and places a huge burden on the health system. Gastrodia elata Blume (GE), a food of medicine–food homology, has been reported to have the ability to inhibit glycosidase activity, indicating its potential in the treatment of diabetes. However, the main pharmacological components of GE for the treatment of T2DM have not been fully clarified. Therefore, this study aims to clarify the pharmacological components changes of GE with different drying methods and the treatment of T2DM using HPLC, network pharmacology, molecular docking and experimental evaluations. The results showed that the GE samples processed by the steam-lyophilized method possessed the highest total content of the six marker components and the strongest antioxidant and α-glucosidase inhibitory abilities. Meanwhile, the six marker compounds had a total of 238 T2DM-related gene targets. Notably, these active compounds have good affinity for key gene targets associated with T2DM signaling pathways. In conclusion, this study revealed that different drying methods of GE affect the content of its major active compounds, antioxidant capacity, α-glucosidase inhibitory capacity and potential pharmacological effects on T2DM, indicating that it is a potential treatment of T2DM.

Abstract Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

To better understand the structure-activity relationship and enhance the overall performance of polymer-bonded explosives (PBXs), the neutron and X-ray scattering techniques, which utilize neutron or X-ray radiation as probes, are unique and useful methods for quantifying the inherent hierarchical microstructures and components of PBXs. This review focuses on a series of scattering techniques and their typical applications in PBXs and includes a brief introduction of large neutron and X-ray scientific facilities in China. It describes the basic principles, instrumentation, sample environment, and empirical approaches of small-angle scattering (SAS), neutron reflection (NR), and neutron diffraction (ND). Additionally, it reviews common applications of these scattering techniques in the fields of PBXs. Combining the scattering techniques with complementary methods yields several valuable parameters that account for the microstructural features of PBXs. The combination can be used to establish multi-scale structure-activity relationships of PBXs and optimize the preparation process, numerical simulations, and performance prediction of PBXs. More efforts should be made to (1) gather the comprehensive multi-scale microstructural parameters for certain PBXs and add them to corresponding characteristic databases; (2) further investigate the dependence of the microstructural features on the preparation conditions of PBXs; (3) establish multi-factor correlations between the multi-scale microstructural features and the multiple performances obtained from experiments; (4) incorporate the microstructural parameters into various theoretical computational models.

E-wallet, also referred to as digital wallet, is a software application designed to replace physical wallets, with the primary purpose of facilitating online transactions when users wish to make virtual payments. Nowadays, E-wallets are not limited to mobile applications, but they have also been extended to wearable devices, such as smartwatches, enabling users to make payments via their watches. This research study focuses on three main E-wallet service providers in Malaysia, namely TouchNGo E-wallet, Boost, and Grab pay, as they are the top three E-wallets in the country. The aim of this paper is to explore the real-world implementation of E-wallets among mobile phone users in Malaysia, employing the Technology Adoption Model as the theoretical framework. Six independent variables were identified to study the implementation of E-wallets, and a total of 500 respondents shared their opinions on retaining the usage of E-wallet in Malaysia. The data collected were analysed using SPSS for Pearson Correlation Analysis and Multiple Linear Regression. Out of the six variables, five independent variables were accepted, and one independent variable was rejected due to the greater significant level. The highest correlation coefficient falls under Business Resources with 0.704. The study delves into the implications and constraints, providing insights for the future advancement of E-wallets within the Malaysian context.

Abstract Objective: This scoping review aimed to systematically map and describe the existing evidence regarding the knowledge, attitudes and practices of health professionals with regard to plant-based diets during pregnancy and to highlight areas for further research. Design: Following a pre-registered protocol, online databases were searched using a comprehensive search string, in addition to selected grey literature sources, and reference lists of included studies. The studies were independently screened for eligibility by two authors, SM and JM. Data from all eligible studies were charted by the first author, and a narrative summary was performed. Setting: Maternal health care services. Results: Ten studies were included for review, from New Zealand (n 2), Australia (n 2), Germany, Netherlands, United Kingdom, France, Italy and Peru. Most of these studies were observational, employed various validated and non-validated survey instruments, interviews and one education intervention. Knowledge was the most frequently assessed outcome in the reviewed studies. Health professionals’ knowledge of plant-based nutrition in pregnancy was reported to be limited and frequently attributed to a lack of nutrition training. Participants’ personal dietary patterns and work specialisation appear to be closely associated with their knowledge, attitudes and practices regarding plant-based diets. Conclusion: This review identified a significant research gap regarding health professionals’ practices in relation to plant-based diets during pregnancy. Additionally, this review has demonstrated the need for further research, awareness and practice protocols to promote high-quality care and education or professional development to address the prevalent lack of knowledge among this group.

BackgroundFriedman's standards, developed almost 50 years ago, may no longer align with the needs of today's obstetric population and current pregnancy management practices. This study aims to analyze contemporary labor patterns and estimate labor duration in China, focusing on first-stage labor data from Chinese parturients with a spontaneous onset of labor.MethodsThis retrospective observational study utilized data from electronic medical records of a tertiary hospital in Changsha, Hunan. Out of a total of 2,689 parturients, exclusions were made for multiple gestations, preterm, post-term, or stillbirth, cesarean delivery, non-vertex presentation, and neonatal intensive care unit admission. Average labor curves were constructed by parity using repeated-measure analysis, and labor duration was estimated through interval-censored regression, stratified by cervical dilation at admission. We performed an analysis to assess the impact of oxytocin augmentation and amniotomy on labor progression and conducted a sensitivity analysis using women with complicated outcomes.ResultsNulliparous women take over 180 minutes for cervical dilation from 3 to 4 cm, and the duration from 5 to 6 cm exceeds 145 minutes. Multiparous women experience shorter labor durations than nulliparous. Labor acceleration is observed after 5 cm in nulliparous, but no distinct inflection point is evident in the average labor curve. In the second stage of labor, the 95th percentile for nulliparous, with and without epidural analgesia, is 142 minutes and 127 minutes, respectively.ConclusionsThese findings provide valuable insights for the reassessment of labor and delivery processes in contemporary obstetric populations, including current Chinese obstetric practice.

Abstract Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

Rose roxburghii, a horticulturally significant species within the Rosa genus of the Rosaceae family, is renowned for its abundance of secondary metabolites and ascorbate, earning it the title ‘king of vitamin C’. Despite this recognition, the mechanisms underlying the biosynthesis and regulation of triterpenoid compounds in R. roxburghii remain largely unresolved. In this study, we conducted high-performance liquid chromatography profiling across various organs of R. roxburghii, including fruit, root, stem, and leaves, revealing distinct distributions of triterpenoid compounds among different plant parts. Notably, the fruit exhibited the highest total triterpenoid content, followed by root and stem, with leaf containing the lowest levels, with leaf containing the lowest levels. Transcriptomic analysis unveiled preferential expression of members from the cytochrome P450 (CYP) and glycosyltransferase (UGT) families, likely contributing to the higher accumulation of both ascorbate and triterpenoid compounds in the fruits of R. roxburghii compared to other tissues of R. roxburghii. Transcriptomic analysis unveiled a potential gene network implicated in the biosynthesis of both ascorbate and triterpenoid compounds in R. roxburghii. These findings not only deepen our understanding of the metabolic pathways in this species but also have implications for the design of functional foods enriched with ascorbate and triterpenoids in R. roxburghii.

Bacterial infections impede the wound healing process and can trigger local or systemic inflammatory responses. Therefore, there is an urgent need to develop a dressing with antimicrobial and anti-inflammatory properties to promote the healing of infected wounds. In this study, BA/COs/NO-PL/AL hydrogels were obtained by adding brevilin A (BA) camellia oil (CO) submicron emulsion and nitric oxide (NO) to hydrogels consisting of sodium alginate (AL) and Pluronic F127 (PL). The hydrogels were characterized through dynamic viscosity analysis, differential scanning calorimetry, and rheology. They were evaluated through anti-inflammatory, antimicrobial, and wound healing property analyses. The results showed that BA/COs/NO-PL/AL hydrogels were thermo-responsive and had good ex vivo and in vivo anti-inflammatory activity, and they also exhibited strong antimicrobial activity against methicillin-resistant Staphylococcus aureus Pseudomonas aeruginosa (MRPA) and methicillin-resistant Staphylococcus aureus (MRSA). They were able to effectively promote healing of the infected wound model and reduce inflammation and bacterial burden. H&E and Masson’s staining showed that BA/COs/NO-PL/AL hydrogels promoted normal epithelial formation and collagen deposition. In conclusion, BA/COs/NO-PL/AL hydrogels are promising candidates for promoting the healing of infected wounds.

Extensive research suggests that COVID-19 infection can lead to persistent changes in taste and smell perception. These sensory changes have the potential to exert lasting impacts on dietary choices, nutrition, and body weight. This study aims to explore COVID-related shifts in dietary intake among New Zealand university students. We conducted a survey involving 340 university students who had experienced COVID-19 infection between 2022 and 2023. Participants reported any changes in eating behavior since before the pandemic and were asked to complete a 24-h food record. Participants’ total daily energy intake, macronutrient intake, and composition were then compared with data collected from a similar cohort before the COVID-19 pandemic, spanning from 2017 to 2019. Dietary outcomes were compared using MANCOVA while controlling for individual age, gender, ethnicity, and BMI. Approximately 25% of participants reported experiencing sensory alterations with COVID-19, with those participants more likely to report changes in their experience of sweet tastes but not salty or fatty foods. Analyses of the pre- and post-COVID cohorts revealed that participants in the post-COVID group exhibited significantly higher consumption of protein and sodium. Understanding the long-term impact of COVID-19 infection may offer crucial insights into the role of chemosensory perception in dietary behavior.

Objective: The present study aimed to evaluate the efficacy of a new two-dimensional shear wave elastography (2D-SWE) method using a Siemens ultrasound system and its combination with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for the differential diagnosis of benign and malignant thyroid nodules. Methods: Conventional ultrasound images and 2D-SWE (E-whole-mean and E-stiffest-mean) were prospectively analyzed in 593 thyroid nodules from 543 patients. Nodules were divided into diameter (D) ≤10 mm and D > 10 mm groups and graded using ACR TI-RADS. The receiver operating characteristic curve was plotted using pathological findings as the gold standard. Diagnostic performance was compared among 2D-SWE, ACR TI-RADS, and their combination. Results: The area under the curve (AUC) for E-whole-mean was higher than that for E-stiffest-mean (0.858 vs. 0.790, P 10 mm groups (P

Abstract Background Ritodrine hydrochloride, a β2-adrenergic agonist, has been widely used in Asia and Europe to treat preterm labor in pregnant women. It has some typical side effects, such as palpitations, pulmonary edema, and hypokalemia. Here, we report a case of rhabdomyolysis and psychiatric symptoms might be associated with intravenous ritodrine. Case presentation A 32-year-old Chinese primigravida woman who was pregnant with twins by in vitro fertilization-embryo transfer was diagnosed with placenta previa and threatened abortion at 21 gestational weeks (GW). The patient was then treated with ritodrine hydrochloride. The initial dose of ritodrine was 150 μg/min, gradually increasing to 360 μg/min at 235/7 GW and 400 μg/min at 271/7 GW. Magnesium sulfate was added to the ritodrine regimen at 215/7 GW in dosage of 1-2 g/h. Psychiatric symptoms appeared at 245/7, 265/7, and 273/7 GW, manifesting as depression, anxiety, and suicidal tendencies. Severe muscle pain in her limbs and general weakness appeared after six weeks of ritodrine administration, which might have been a sign of rhabdomyolysis resulting from ritodrine administration. After ceasing the administration of ritodrine, the muscle pain and relevant data from laboratory tests on the patient were significantly improved, and her mood was stable. It is worth noting that this is the first time to report psychiatric symptoms may associated with the administration of ritodrine. In addition, we reviewed and analyzed six reported cases of rhabdomyolysis caused by ritodrine. Conclusion Our results suggest that we should pay more attention to the risk of rhabdomyolysis and psychiatric symptoms induced by intravenous ritodrine hydrochloride, especially in patients with a history of neuromuscular disorder, or concomitant use of magnesium sulfate.

Extraction process for Q-markers from Rosa roxburghii using response surface methodology was optimized and HPLC method was established for simultaneous determination of their content. The extraction process of Q-marker from the root of Rosa roxburghii Tratt was optimized by single factor experiments and response surface methodology, and the four Q-markers (triterpenoids) in different parts (root, stem, leaf and fruit) of Rosa roxburghii Tratt were analyzed. Results showed that, through single factor experiments, the important factors affecting the yield of Q-markers were determined as solvent dosage, ethanol concentration, extraction time and extraction times. Response surface methodology was used to optimize the extraction process of Q-markers from Rosa roxburghii. The optimal extraction conditions were as follows: The solvent dosage was 1:25 g/mL, 70% ethanol was added, the extraction time was 30 min, and then the material was refluxed for 2 h. The yield of four Q-markers from the Rosa roxburghii leaves was 2.64%, including 0.99% of Kaji-ichigoside F1, 0.72% mg/g of rosamultin, 0.43% of rosolic acid and 0.51% of 2α,19α-dihydroxyursolic acid. The total content of Q-markers in different parts of Rosa roxburghii Tratt was in the order of leaves, roots, stems and fruits. This study would provide scientific reference for quality evaluation of Rosa roxburghii and development and utilization of total triterpenoids.

Background: Despite the increasing reports of re-positive SARS-CoV-2 cases after recovery and discharge from hospitals, our knowledge remains very limited regarding the contributing factors of re-positivity and its roles in the transmission and epidemiology of the Omicron variant. Methods: In this retrospective study, re-positivity is defined as the positive nucleic acid result (Ct

PurposeSpermatogonial stem cells (SSCs) are essential for maintaining reproductive function in males. B-lymphoma Mo-MLV insertion region 1 (BMI1) is a vital transcription repressor that regulates cell proliferation and differentiation. However, little is known about the role of BMI1 in mediating the fate of mammalian SSCs and in male reproduction. This study investigated whether BMI1 is essential for male reproduction and the role of alpha-tocopherol (α-tocopherol), a protective agent for male fertility, as a modulator of BMI1 both in vitro and in vivo.MethodsMethyl thiazolyl tetrazolium (MTT) and 5-ethynyl-2′-deoxyuridine (EDU) assays were used to assess the effect of BMI1 on the proliferative ability of the mouse SSC line C18-4. Real-time polymerase chain reaction (PCR), western blotting, and immunofluorescence were applied to investigate changes in the mRNA and protein expression levels of BMI1. Male mice were used to investigate the effect of α-tocopherol and a BMI1 inhibitor on reproduction-associated functionality in vivo.ResultsAnalysis revealed that BMI1 was expressed at high levels in testicular tissues and spermatogonia in mice. The silencing of BMI1 inhibited the proliferation of SSCs and DNA synthesis and enhanced the levels of γ-H2AX. α-tocopherol enhanced the proliferation and DNA synthesis of C18-4 cells, and increased the levels of BMI1. Notably, α-tocopherol rescued the inhibition of cell proliferation and DNA damage in C18-4 cells caused by the silencing of BMI1. Furthermore, α-tocopherol restored sperm count (Ctrl vs. PTC-209, p = 0.0034; Ctrl vs. PTC-209 + α-tocopherol, p = 0.7293) and normalized sperm malformation such as broken heads, irregular heads, lost and curled tails in vivo, as demonstrated by its antagonism with the BMI1 inhibitor PTC-209.ConclusionAnalysis demonstrated that α-tocopherol is a potent in vitro and in vivo modulator of BMI1, a transcription factor that plays an important role in in SSC proliferation and spermatogenesis. Our findings identify a new target and strategy for treating male infertility that deserves further pre-clinical investigation.

Abstract A major reason for the high mortality of patients with bladder cancer (BC) is that chemotherapy and surgery are only effective for very limited patients. Thus, developing novel treatment options becomes an urgent need for improving clinical outcomes and the quality of life for BC patients. Here, we demonstrated that proguanil significantly inhibited the growth of BC in vitro and in vivo. Importantly, our results indicated that the sensitivity of BC cells to proguanil is positively correlated with the expression of epidermal growth factor receptor (EGFR). Mechanistically, proguanil specifically targeted EGFR and promoted EGFR binding to Caveolin-1, enhanced its endocytosis in a Clathrin-independent manner, and then recruited c-Cbl to promote EGFR ubiquitination and degradation through the lysosomal pathway. Further studies suggested that proguanil induced autophagy by destabilizing EGFR and inhibiting its downstream signaling pathway. Thus, this study reveals the novel mechanism of proguanil on anticancer activity and implies the potential benefits of this drug in the treatment of BC.

Our previous study found that the intravesical perfusion of metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel formulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong inhibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and the expression of tumor biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPKα/mTOR signaling pathway compared with metformin alone. These findings aim to make this novel formulation an efficient candidate for managing BC via intravesical administration.

We aimed to explore whether the effect of progesterone on preeclampsia via the PI3K/AKT signaling pathway. First, we studied the role of progesterone in preeclampsia patients and HTR-8/Svneo cells by adding progesterone. Then PI3K inhibitor LY294002 was added. The effects of progesterone on preeclampsia were also studied in animals by constructing a preeclampsia rat model. CCK-8 and Transwell assay were applied to measure cell viability and invasion ability. ELISA was performed to measure progesterone, MMP-2, MMP-9, pro-inflammatory factors TNF-α, IL-1β, and anti-inflammatory factors IL-4, IL-10, and IL-13 levels. HE staining was used to detect the pathological changes in uterine spiral artery. Western blot was performed to detect Cyclin D1, PCNA, MMP-2, MMP-9, inflammatory factors TNF-α, IL-1β, IL-4, IL-10, IL-13, and PI3K/AKT signaling pathway related proteins AKT, p-AKT, PI3K, and p-PI3K expressions. Progesterone could reduce blood pressure and urine protein in pregnant women with preeclampsia. TNF-α and IL-1β levels were decreased, but IL-4, IL-10, IL-13, cyclin D1, and PCNA levels were increased in pregnant women with preeclampsia after using progesterone. After the use of progesterone, the symptoms of the PE model group were improved. Among them, the lumen of the placental uterine spiral artery was enlarged, and the fibrinoid necrosis of the uterine wall and acute atherosclerotic lesions were relieved. In addition, progesterone promoted HTR-8/Svneo cells proliferation and invasion. However, high expression of MMP-2, MMP-9, p-AKT, and p-PI3K in Normal and preeclampsia groups caused by progesterone was weakened after adding LY294002, indicating that progesterone could activate PI3K/AKT signaling pathway to regulate HTR-8/Svneo cells. Progesterone decreased urine protein and blood pressure of preeclampsia rats in a concentration-dependent manner. Moreover, progesterone activated the PI3K/AKT signaling pathway and inhibited the inflammatory response in preeclampsia rats.

In recent decades, it has been uncovered that the autonomic nervous system (ANS) can be influenced using non-contact neuromodulation via odor stimulation. Increasing parasympathetic-vagal activation of the ANS is integral to improving the sympathovagal balance between the sympathetic- and parasympathetic nervous systems, which is often imbalanced in several chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Although research into olfactory stimulation has been observed on the ANS, it is still lacking in the exploration of odor concentration and odor-specific effects. This is particularly the case as research has not utilized specified tools, such as the olfactometer to provide precise odor delivery. Furthermore, no research has compared the results in separate sex cohorts to investigate the role of sex or the menstrual stage on the subsequent interactions. In this study, we investigated the olfactory stimulation effects of four natural odors (mushroom, lavender, jasmine, and rose) in three concentrations (low, moderate, and high) on the ANS. To observe activity from the ANS, we used an electrocardiogram (ECG) based heart rate variability (HRV) and eye-tracker technology (pupil diameter). We found for the first time in literature that there were acute dose- and duration-specific odor effects of odors on the ANS. We also found sex and menstrual cycle effects in this interaction. Furthermore, there were stark distinctions in sympathovagal activity dependent ANS activation (HRV) in comparison to the oculomotor nerve-parasympathetic/cervical sympathetic nerves dependent ANS responses (pupil diameter). Sympathovagal activity dependent HRV showed odor, sex, and menstrual-stage interactions in both divisions of the ANS while the pupil responses only indicated increased sympathetic activation. These results shed light on the use of odor-specific stimulation to modulate the ANS activity in the context of sex and the menstrual stage. Future studies should be performed using a chronic odor delivery design to investigate the long-term effects of odors on the ANS.Clinical trial registrationAustralian New Zealand Clinical Trials Registry, identifier [ACTRN12622000415707].

Oral niacinamide mononucleotide (NMN) and aerobic exercise have been shown to enhance niacinamide adenine dinucleotide (NAD+) in the body. NAD+ plays a critical role in the body and can directly and indirectly affect many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cell aging, and immune cell function. It is noteworthy that the level of NAD+ decreases gradually with increasing age. Decreased levels of NAD+ have been causally associated with a number of diseases associated with aging, including cognitive decline, cancer, metabolic diseases, sarcopenia, and frailty. Many diseases related to aging can be slowed down or even reversed by restoring NAD+ levels. For example, oral NMN or exercise to increase NAD+ levels in APP/PS1 mice have been proven to improve mitochondrial autophagy, but currently, there is no regimen combining oral NMN with exercise. This review summarizes recent studies on the effect of oral NMN on the enhancement of NAD+ in vivo and the improvements in mitochondrial autophagy abnormalities in AD through aerobic exercise, focusing on (1) how oral NMN improves the internal NAD+ level; (2) how exercise regulates the content of NAD+ in the body; (3) the relationship between exercise activation of NAD+ and AMPK; (4) how SIRT1 is regulated by NAD+ and AMPK and activates PGC-1α to mediate mitochondrial autophagy through changes in mitochondrial dynamics. By summarizing the results of the above four aspects, and combined with the synthesis of NAD+ in vivo, we can infer how exercise elevates the level of NAD+ in vivo to mediate mitochondrial autophagy, so as to propose a new hypothesis that exercise interferes with Alzheimer’s disease (AD).

Abstract Postpartum Depression (PPD) is the most common non-obstetric complications associated with childbearing, but currently has poor diagnostic regimes. Sensory symptoms of PPD are understudied, particularly with regard to the sense of olfaction. The present study addresses this research gap by assessing differences in olfactory abilities between 39 depressed mothers, who were within the perinatal period (i.e., during pregnancy and up to 1-year post pregnancy) and assessed with Edinburgh Postnatal Depression Scale, and their case-matched healthy volunteers. The assessments include two olfactory testing sessions conducted 4-weeks apart, each comprising a standard odour detection threshold test (i.e., Snap & Sniff Olfactory Test System), and intensity and valence ratings for 3 “pleasant” and 3 “unpleasant” odorants. The results revealed no difference between patients (M = 5.6; SE = 0.3) and control group (M = 5.7; SE = 0.4) in terms of olfactory detection threshold. However, the patients group perceived the 3 “unpleasant” odours as significantly less pleasant (p

Recent studies show that visual exposure to different portion sizes can lead to portion alterations in subsequent meals, suggesting that manipulations of tableware sizes may also modify portion size perception and downstream eating behaviour. The present study aims to address this novel question by testing 61 male participants (20–40 years; 19.7–41.5 kg·m−2) over three breakfast sessions in a controlled laboratory. In each session, the participant was served a pre-determined breakfast portion in either medium (control; CT), small (SC), or large (LC) jars. Participants were asked to rate post-meal satiety, and then recorded food intake for the rest of the day using Food Records. Our results indicated significant changes in post-meal satiety following the SC or LC condition, compared to CT (SC: 55.3 ± 10.8, LC: 31.0 ± 8.4, CT: 42.1 ± 9.6, F(2, 108) = 25.22, p < 0.001). SC led to a reduction in post-breakfast energy intake (F(2, 108) = 61.28, p < 0.001), but was counteracted by a substantial increase in downstream intake at the following meal (F(2, 108) = 47.79, p < 0.001), resulting in an overall increase in total daily energy intake (F(2, 108) = 11.45, p < 0.001). This study provides the first evidence that small tableware may not be a long-term solution for addressing overeating and related health issues (e.g., obesity), reinforcing the importance of considering downstream intake in eating-related intervention.

AIM: To analyze the therapeutic effects of anti-vascular endothelial growth factor(VEGF)drugs on patients with macular edema secondary to central retinal vein occlusion(CRVO-ME)in different age groups.METHODS: The study retrospectively reviewed 102 patients(102 eyes)with CRVO-ME treated with intravitreal injection of ranibizumab in ophthalmology department of the hospital between February 2017 and March 2019. The subjects were divided into CM1 group(under 50 years old, 50 cases, 50 eyes)and CM2 group(50 years old or older, 52 cases, 52 eyes), and were followed up for 12mo after treatment. The best corrected visual acuity(BCVA), central macular thickness(CMT), intraocular pressure, average injection times, first injection interval, and complications were recorded.RESULTS: After treatment, the BCVA of both groups was improved, and the CMT decreased. Besides, CM1 group had better BCVA and CMT than CM2 group at 9mo and 12mo(PPPP>0.05). Additionally, CM1 group had lower intraocular pressure than CM2 group at 1mo, 2mo, and 3mo after treatment(PPCONCLUSION: The treatment with anti-VEGF drugs(ranibizumab)for CRVO-ME can significantly improve the patients' visual acuity, and reduce CMT. The condition can be significantly improved within 1mo after injection, without significant influence on intraocular pressure. Compared with patients over 50 years old, patients under 50 years old can obtain better results after treatment with ranibizumab, more significant improvement of visual acuity, significantly thinner CMT, smaller intraocular pressure fluctuations and shorter first injection interval.

The peptide hormones ghrelin and leptin play major roles in the regulation of appetite and food intake. However, the precise effects of these hormones on sensory processing remain a subject of debate, particularly with food related stimuli and its small body of evidence. Here, we test for relationships between ghrelin and leptin levels against olfactory performance with multiple food-related odours. Specifically, a total of 94 Caucasian males were tested for their supra-threshold sensitivity (i.e., d′), intensity, and valence perception to three odour compounds (i.e., vanilla, potato, and dairy odours). These sensory data were then analysed against peripheral ghrelin and leptin levels, both assessed in plasma samples. Participants’ body adiposity measures were also obtained. Results lent strong support to one of our original hypotheses, with ghrelin levels being positively correlated to the supra-threshold sensitivity of the dairy odour, (r = 0.241, p = 0.020), and intensity ratings to most of the food odours tested [dairy (r = 0.216, p = 0.037) and vanilla (r = 0.241, p = 0.020)]. By contrast, peripheral leptin levels were not significantly linked to any of the olfactory measures (p > 0.05). These relationships remained similar after controlling for variabilities of adiposity measures. The present study brings novel insights by identifying positive links between supra-threshold olfactory perception and ghrelin. This new knowledge is highly relevant for future research linking olfactory shifts to hormonal dysregulation and obesity.

Humans and a wide range of mammals are generally susceptible to Schistosoma infection, while some rodents such as Rattus rats and Microtus spp are not. We previously demonstrated that inherent high expression levels of nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), plays an important role in blocking the growth and development of Schistosoma japonicum in wild-type rats. However, the potential regulatory effects of NO on the immune system and immune response to S. japonicum infection in rats are still unknown. In this study, we used iNOS-knockout (KO) rats to determine the role of iNOS-derived NO in the immune system and immunopathological responses to S. japonicum infection in rats. Our data showed that iNOS deficiency led to weakened immune activity against S. japonicum infection. This was characterized by the impaired T cell responses and a significant decrease in S. japonicum-elicited Th2/Th1 responses and cytokine and chemokine-producing capability in the infected iNOS-KO rats. Unlike iNOS-KO mice, Th1-associated cytokines were also decreased in the absence of iNOS in rats. In addition, a profile of pro-inflammatory and pro-fibrogenic cytokines was detected in serum associated with iNOS deficiency. The alterations in immune responses and cytokine patterns were correlated with a slower clearance of parasites, exacerbated granuloma formation, and fibrosis following S. japonicum infection in iNOS-KO rats. Furthermore, we have provided direct evidence that high levels of NO in rats can promote the development of pulmonary fibrosis induced by egg antigens of S. japonicum, but not inflammation, which was negatively correlated with the expression of TGF-β3. These studies are the first description of the immunological and pathological profiles in iNOS-KO rats infected with S. japonicum and demonstrate key differences between the responses found in mice. Our results significantly enhance our understanding of the immunoregulatory effects of NO on defensive and immunopathological responses in rats and the broader nature of resistance to pathogens such as S. japonicum.

We report herein an efficient protocol for the synthesis of 4-vinylphenols by a catalyst-free decarboxylation of trans-4-hydroxycinnamic acids. A variety of 4-vinylphenols has been synthesized in moderate to excellent yields. This protocol also features no polymerization.

A pairwise coupling of 0D Super-P (SP), 1D carbon nanotubes (CNTs), and 2D graphene nanosheets (GNs) into binary carbon-based conductive additives was used here for the LiFePO4 cathode in lithium-ion batteries. For comparison, the LiFePO4 cathode with SP, CNT, or GN unitary conductive agent was also examined. Electrochemical test results suggest that the cathodes with binary conducting additives present greatly improved electrochemical performance than the traditional cathode system (only SP used). Especially, the LiFePO4 cathode containing 3% CNT component exhibits the highest specific capacity and the best cycling stability among all the cathodes with binary conducting additives, indicating that an appropriate amount of CNTs is critical in enhancing the conductivity and practical capacity output. However, an excess of CNTs leads to entangling with each other, hampering the uniform distribution of active materials and resulting in poor electrode performance. Furthermore, the combination of CNT and GN can effectively improve the capacity and cycling stability of the LiFePO4 cathodes due to the synergistic effect of 3D conductive networks constructed by the two.

Recently, a robust and secure image sharing scheme with personal identity information embedded was proposed based on Compressive Sensing, Secret Image Sharing and Diffie-Hellman Agreement. However, there exists a security flaw in this scheme. It cannot resist the man-in-the-middle attack in the authentication stage. Anyone can disguise himself as a legal person and get the information when exchanging the secret keys, which provides the possibility for information leakage, tampering, and other attacks. In this paper, we propose an image encryption and compression algorithm with identity authentication and blind signcryption based on Parallel Compressive Sensing (PCS), Secret Sharing(SS) and Elliptic Curve Cryptography (ECC). Firstly, Logistic-Tent system and PCS are employed to complete compression and lightweight encryption in the compression stage. Secondly, random sequences are generated based on Chebyshev map to construct four encryption matrices to perform the encryption process. Meanwhile, the participants' identity authentication and blind signcryption can be achieved by using ECC. Finally, we prove the efficiency and security of the blind signcryption, which can authenticate the participants' identity before restoring the original image. Experiments and security analysis demonstrate that the proposed scheme not only reduce the storage space and computational complexity effectively, but also has resistance against the man-in-the-middle attack, forgery attack and chosen-text attack.

Background: This study explored the guiding value of monitoring pregnancy-induced hypertension syndrome (MP) for blood hypercoagulability in combination with ultrasound monitoring of uterine artery blood flow in early pregnancy and fetal growth and development in the second and third trimesters, with the goal of preventing chronic hypertension with preeclampsia (PE) and its clinical effects. Methods: The medical records of 189 pregnant patients with chronic hypertension between June 2016 and June 2021 were retrospectively analyzed; among them, 98 constituted the intervention group. The intervention group received MP screening for blood hypercoagulability in combination with ultrasound monitoring of uterine artery blood flow in early pregnancy and fetal growth and development in the second and third trimesters of pregnancy. Those with abnormalities were given timely symptomatic (low-molecular-weight heparin with or without aspirin) and supportive treatment. The remaining 91 patients who did not receive timely monitoring and intervention constituted the control group. Fetal outcomes and PE rates were compared between groups. Results: The PE incidence in the intervention group was significantly lower than that in the control group (p < 0.01), and the premature delivery of low-birth-weight neonates, fetal loss and neonatal asphyxia incidences were also significantly lower in the intervention group than the control group (p < 0.05). Conclusions: MP screening for blood hypercoagulability combined with ultrasound monitoring of uterine artery blood flow can effectively prevent PE occurrence in pregnant patients with chronic hypertension and significantly improve fetal outcomes. Additionally, MP screening is noninvasive and easy to use at a low cost.

The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of influenza A viruses, and it is able to elicit protective immunity against the viruses. The influenza nucleoprotein (NP) was used to display the M2e in this study due to its promising T-cell response and adjuvanticity. The M2e gene was fused to the 5′-end of the NP gene and then cloned into pRSET B vector. The DNA sequencing analysis revealed six point mutations in the M2e-NP fusion gene, including one mutation in the M2e peptide and five mutations in the NP. The mutations were reverted using PCR site-directed mutagenesis. The recombinant plasmids (pRSET B-M2e-NP and pRSET B-mM2e-NP) were introduced into Escherichia coli (E. coli) BL21 (DE3) for protein expression. The mutated and non-mutated proteins were subsequently expressed and named mM2e-NP and M2e-NP, respectively. The expression of mM2e-NP and M2e-NP was not affected by the mutations. The binding of anti-M2e antibody to the purified native mM2e-NP and M2e-NP also remained active. However, when the anti-NP antibody was tested, the signal produced by mM2e-NP was very weak. The results implied that the amino acid changes in the NP had adversely impacted on the conformation of mM2e-NP and subsequently affected the antibody binding. In light of the remarkable antibody binding to the M2e-NP fusion protein, this study highly recommends the potential of M2e-NP as a universal influenza vaccine candidate.

Background Fructus Rose roxburghii is a popular edible fruit with high nutritional and medicinal value, which was effective on anti-alcohol and liver-protection in southwest China.Purpose The aim of this study was to determine main chemical composition of the extract enriched in triterpenoids from Fructus R. roxburghii (TFRr) using UPLC-MS/MS and to investigate the hepatoprotective effects and molecular mechanisms of TFRr in mice with alcohol-induced liver injury.Methods TFRr were isolated from 75% ethanol extract of Fructus R. roxburghii and chemical constituents of TFRr were analyzed using UPLC-MS/MS. Male Kun-Ming mice were randomly divided into two experimental groups (TFRr groups (50 mg/kg) and TFRr groups (100 mg/kg)) and two control groups (normal control group and 53% ethanol group). Liver injury in mice was induced by oral administration with Lieber-DeCarli liquid diet mixing with 53% ethanol. After 10 days of treatment, the mice were weighed and treated with inhaling diethyl ether to anesthetize, then, the blood and liver tissue samples were gathered for molecular analysis and histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice serum and the superoxide dismutase (SOD) activity, glutathione peroxidase (GSH) activity and malondialdehyde (MDA) levels in mice liver were detected by Elisa kits. Western blot analysis was carried out to detect the protein expression levels of nuclear factor-erythroid-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), SOD1, glutathione S-transferase (GST) and Keap1 in liver tissues.Results Five triterpenoids (kaji-ichigoside F1, rosamultin, tormentic acid, roxburic acid, and pomonic acid) from TFRr extract were identified. TFRr treatment diminished the effects of LPS on the serum levels of AST and ALT in mice as well as MDA, SOD and GSH in liver. In addition, the protein expression levels of Nrf2 target genes, consisting of HO-1, SOD1, GST, GCLM, and GCLC were significantly upregulated by TFRr suggesting TFRr significantly attenuates the alcohol-induced liver injury by Keap1-Nrf2 signaling pathway.Conclusions These results show TFRr has the profoundly protective roles against ethanol-induced liver injury in mice models via Nrf2-Keap1 signaling pathway. Our results suggested that it is rationale to explore the application of extract enriched with active triterpenoids from Fructus Rosa roxburghii in the development of liver protectants.

Abstract Background Potent granulomatous inflammation responses induced by schistosome eggs and resultant fibrosis are the primary causes of morbidity in schistosomiasis. Recombinant Sj16 (rSj16), a 16-kDa protein of Schistosoma japonicum produced in Escherichia coli, has been demonstrated to have novel immunoregulatory effects in vivo and in vitro. Thus, this study investigated the anti-inflammatory and anti-fibrotic effects of rSj16 treatment in S. japonicum-infected mice and demonstrated the immune modulation between the schistosome and the host. Methods Schistosoma japonicum infected mice were treated with the rSj16 protein and Sj16 peptide at different time points post-infection to assess their efficacy at the optimal time point. Sj16 peptide and/or Praziquantel (PZQ) treatments were initiated at week 5 post-infection to compare the therapeutic efficacy of each regimen. Hepatic granulomatous inflammation, fibrosis and cytokine production (pro-inflammatory, Th1, Th2, Th17 and regulatory cytokines IL-10) were detected. Moreover, M2 macrophages were measured to illuminate the mechanisms of Sj16. Results The rSj16 protein and Sj16 peptide had significant protective effects in S. japonicum-infected mice, as shown by decreased granuloma formation, areas of collagen deposition and inhibition of pro-inflammatory Th1, Th2 and Th17 cytokine production. These protective activities were more obvious when animals were treated with either the Sj16 protein or peptide at early stages post-infection. Interestingly, the combined treatment of PZQ and Sj16 was more effective and upregulated IL-10 production than administration of PZQ alone in infected mice. Furthermore, the Sj16 treatment alleviated the pathological effects associated with activated M2 macrophages. Conclusions This study demonstrates the anti-inflammatory and anti-fibrotic effects of rSj16 in schistosomiasis. Therefore, the combination of rSj16 with PZQ could be a viable and promising therapeutic strategy for schistosomiasis. In addition, this investigation provides additional information on schistosome-mediated immune modulation and host-parasite interactions.

We consider a 2nth-order nonlinear difference equation containing both many advances and retardations with p-Laplacian. Using the critical point theory, we obtain some new explicit criteria for the existence and multiplicity of periodic and subharmonic solutions. Our results generalize and improve some known related ones.

Endoplasmic reticulum stress (ER stress) can be induced when cellular protein homeostasis is damaged, and cells can activate the unfolded protein response (UPR) to restore protein homeostasis or induce cell death to facilitate the survival of the whole system. Globally, parasites are a constant threat to human health and are therefore considered a serious public health problem. Parasitic infection can cause ER stress in host cells, and parasites also possess part or all of the UPR under ER stress conditions. In this review, we aim to clarify the role of ER stress pathways and related molecules in parasites for their survival and development, the pathogenesis of parasitosis in hosts, and the artemisinin resistance of Plasmodium, which provides some potential drug design targets to inhibit survival of parasites, relieves pathological damage of parasitosis, and solves the problem of artemisinin resistance.

Bladder cancer is the ninth most frequently diagnosed cancer world-wide and ranks 13th in cancer-related deaths. Two tremendous breakthroughs in bladder cancer therapy over the last decades are the approval of immune checkpoint inhibitors(ICIs)and the fibroblast growth factor receptor tyrosine kinase inhibitor (FGFR-TKI) erdafitinib for treating this deadly disease. Despite the beneficial effects of these approaches, the low response rate and the potential resistance of the cancer are major concerns. Hence, novel combination therapies to overcome these limitations have been investigated. In this context, combining immunotherapy with targeted drugs is an appealing therapeutic option to improve response and reduce the emergence of resistance in the management of bladder cancer. In this review, the rationale of using different therapeutic combinations is discussed according to the mechanistic differences, emphasizing the efficacy and safety based on evidence collected from preclinical and clinical studies. Finally, we highlight the limitations of these combinations and provide suggestions for further efforts in this challenging field.

Snacking is a common eating habit in the modern food environment. Individual snack choices vary substantially, with sweet versus savoury snacks linked to differential health outcomes. The role of olfactory and gustatory sensitivities in snack choices and consumption is yet to be tested. A total of 70 Caucasian young males (age: 21–39 years; BMI: 20.5–40.5 kg∙m−2) were tested for their supra-threshold sensitivities to sweet and savoury associated odours and tastants (vanillin, methional; sucrose, NaCl). The participants also attended an ad libitum task in which their intakes of sweet and savoury snacks were recorded and analysed. Univariate and multivariate analyses were used to test for relationships between odour/taste sensitivities and sweet versus savoury snack intake. Results indicated that individual sensitivities to sweet-associated stimuli (e.g., vanillin, sucrose) were negatively linked with intake of the congruent (e.g., sweet) snacks and positively linked with incongruent (e.g., savoury) snacks (p < 0.05). These differences were reflected by energy intake rather than consumption weight (p > 0.05). This study outlines the fundamental roles of olfactory and gustatory sensitivities in snack choices and offers novel insights into inter-individual variability in snack consumption.

Human schistosomiasis, which is caused by schistosomes, is a zoonosis that is difficult to control because of the many reservoir hosts. However, Microtus fortis is the only mammal that is naturally resistant to Schistosoma japonicum infection known in China, in which S. japonicum growth and development were arrested on day 12, and the worms eliminated on day 20 post-infection. In this review, we present an overview of the established and purported mechanisms of resistance to S. japonicum infection in M. fortis in comparison to Rattus norvegicus, a semi-permissive host. Clarifying the mechanism of this efficient resistance can help us to better understand host-parasite interaction and to provide better methods to control schistosomiasis.

Abstract Background In previous studies, we have shown that the combination of metformin and gefitinib inhibits the growth of bladder cancer cells. Here we examined whether the metformin analogue phenformin, either used alone or in combination with gefitinib, could inhibit growth of bladder cancer cells. Methods The growth-inhibitory effects of phenformin and gefitinib were tested in one murine and two human bladder cancer cell lines using MTT and clonogenic assays. Effects on cell migration were assessed in a wound healing assay. Synergistic action between the two drugs was assessed using CompuSyn software. The potential involvement of AMPK and EGFR pathways in the effects of phenformin and gefitinib was explored using Western blotting. Results In MTT and clonogenic assays, phenformin was > 10-fold more potent than metformin in inhibiting bladder cancer cell growth. Phenformin also potently inhibited cell migration in wound healing assays, and promoted apoptosis. AMPK signaling was activated; EGFR signaling was inhibited. Phenformin was synergistic with gefitinib, with the combination of drugs showing much stronger anticancer activity and apoptotic activation than phenformin alone. Conclusions Phenformin shows potential as an effective drug against bladder cancer, either alone or in combination with gefitinib.

Taste perception plays an undisputed role in food choice, preference, and intake. Recent literature suggests that individual diet and taste sensitivity may have a reciprocal relationship, with evidence highlighting that specific diets can alter taste sensitivities. Commensurate with an increase in the prevalence of plant-based diets is the importance of investigating if following a vegetarian or vegan diet is associated with altered taste sensitivities. In this study, the taste detection thresholds for six compounds (i.e., sweet—sucrose, salty—sodium chloride, sour—citric acid, umami—monosodium glutamate, MSG, bitter—caffeine, and metallic—iron II sulphate heptahydrate) were measured for a total of 80 healthy, New Zealand European females aged 18–45 years old, who were categorised as 22 vegans, 23 vegetarians, and 35 omnivores. Each participant’s detection thresholds to these compounds were measured across two sessions, using an ascending Method of Limits with two-alternative-forced-choice presentations. The threshold data were analysed using both multivariate (i.e., principal component analysis) and univariate (i.e., ANCOVA) techniques to assess differences across the three types of diet. Multivariate analysis suggested that the omnivore group had distinct taste sensitivity patterns across the six compounds compared to the vegetarian or vegan group, which were characterised by relatively heightened sensitivity to metallic and lowered sensitivity to sweetness. Furthermore, the vegetarian group was shown to have a significantly lower detection threshold to bitterness (i.e., caffeine) relative to the other two groups (p < 0.001). While future study is required to investigate the cause–effect relationship between individual diet and taste sensitivities, the present study provides a systematic evaluation of taste sensitivities of individuals following distinct diets. This information may be valuable to future gustatory research as well as to food manufacturers.

Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as Escherichia coli without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.