Advancements and challenges in pharmacokinetic and pharmacodynamic research on the traditional Chinese medicine saponins: a comprehensive review.

Recent research on traditional Chinese medicine (TCM) saponin pharmacokinetics has revealed transformative breakthroughs and challenges. The multicomponent nature of TCM makes it difficult to select representative indicators for pharmacokinetic studies. The clinical application of saponins is limited by their low bioavailability and short half-life, resulting in fluctuating plasma concentrations. Future directions should focus on novel saponin compounds utilizing colon-specific delivery and osmotic pump systems to enhance oral bioavailability. Optimizing drug combinations, such as ginsenosides with aspirin, shows therapeutic potential. Rigorous clinical validation is essential for practical applications. This review emphasizes a transformative era in saponin research, highlighting the need for clinical validation. TCM saponin pharmacokinetics, guided by traditional principles, are in development, utilizing multidisciplinary approaches for a comprehensive understanding. This research provides a theoretical basis for new clinical drugs and supports rational clinical medication.

Temperature fluctuations in mesoscopic systems.

Temperature is a fundamental concept in thermodynamics. In macroscopic thermodynamics, systems possess their own intrinsic temperature which equals the reservoir temperature when they equilibrate. In stochastic thermodynamics for simple systems at the microscopic level, thermodynamic quantities other than temperature (a deterministic parameter of the reservoir) are stochastic. To bridge the disparity in the perspectives about temperature between the micro- and macroregimes, we assign a generic mesoscopic N-body system an intrinsic fluctuating temperature T in this work. We simplify the complicated dynamics of numerous particles to one stochastic differential equation with respect to T, where the noise term accounts for finite-size effects arising from random energy transfer between the system and the reservoir. Our analysis reveals that these fluctuations make the extensive quantities (in the thermodynamic limit) deviate from being extensive. Moreover, we derive finite-size corrections, characterized by heat capacity of the system, to the Jarzynski equality. A possible violation of the principle of maximum work that scales with N^{-1} is also discussed. Additionally, we examine the impact of temperature fluctuations in a finite-size Carnot engine. We show that irreversible entropy production resulting from the temperature fluctuations of the working substance diminishes the average efficiency of the cycle as η_{C}-〈η〉∼N^{-1}, highlighting the unattainability of the Carnot efficiency η_{C} for mesoscopic heat engines even under the quasistatic limit. Our general framework paves the way for further exploration of nonequilibrium thermodynamics and the corresponding finite-size effects in a mesoscopic regime.

The interaction between 20-hydroxyecdysone and AMPK through PI3K activation in Chinese mitten crab, Eriocheir sinensis.

In crustaceans, the steroid hormone 20-hydroxyecdysone (20E) initiates molting, and the molting process is also regulated by energy metabolism. AMPK is an energy sensor and plays a critical role in systemic energy balance. Here, the regulatory mechanism in the interaction between 20E and AMPK was investigated in Chinese mitten crab, Eriocheir sinensis. The results showed that the 20E concentration and the mRNA expression levels of 20E receptors in hepatopancreas were down-regulated post AMPK activator (AICAR) treatment, and were up-regulated after AMPK inhibitor (Compound C) injection in crabs. Besides, the molt-inhibiting hormone (MIH) gene expression in eyestalk showed the opposite patterns in response to the AICAR and Compound C treatment, respectively. Further investigation found that there was a significant reduction in 20E concentration post PI3K inhibitor (LY294002) treatment, and the phosphorylation level of PI3K was increased in hepatopancreas after AMPK inhibitor injection. On the other hand, the positive regulation of PI3K-mediated activation of AMPK was also observed, the phosphorylation levels of AMPKα, AMPKß and PI3K in hepatopancreas were significantly increased post 20E injection. In addition, the phosphorylation levels of AMPKα and AMPKß induced by 20E were decreased after the injection of PI3K inhibitor. Taken together, these results suggest that the regulatory cross-talk between 20E and AMPK is likely to act through PI3K pathway in E. sinensis, which appeared to be helpful for a better understanding in molting regulation.

Robust Dual-Modal Speech Keyword Spotting for XR Headsets.

While speech interaction finds widespread utility within the Extended Reality (XR) domain, conventional vocal speech keyword spotting systems continue to grapple with formidable challenges, including suboptimal performance in noisy environments, impracticality in situations requiring silence, and susceptibility to inadvertent activations when others speak nearby. These challenges, however, can potentially be surmounted through the cost-effective fusion of voice and lip movement information. Consequently, we propose a novel vocal-echoic dual-modal keyword spotting system designed for XR headsets. We devise two different modal fusion approches and conduct experiments to test the system's performance across diverse scenarios. The results show that our dual-modal system not only consistently outperforms its single-modal counterparts, demonstrating higher precision in both typical and noisy environments, but also excels in accurately identifying silent utterances. Furthermore, we have successfully applied the system in real-time demonstrations, achieving promising results. The code is available at https://github.com/caizhuojiang/VE-KWS.

Regulating Metal Centers of MOF-74 Promotes PEO-Based Electrolytes for All-Solid-State Lithium-Metal Batteries.

Poly(ethylene oxide) (PEO)-based electrolytes have been extensively studied for all-solid-state lithium-metal batteries due to their excellent film-forming capabilities and low cost. However, the limited ionic conductivity and poor mechanical strength of the PEO-based electrolytes cannot prevent the growth of undesirable lithium dendrites, leading to the failure of batteries. Metal-organic frameworks (MOFs) are functional materials with a periodic porous structure that can improve the electrochemical performance of PEO-based electrolytes. However, the enhancement effect of MOFs with different metal centers and the interaction mechanism with PEO remain unclear. Herein, MOF-74s with Cu or Ni centers are prepared and used as fillers of PEO-based electrolytes. Adding 15 wt % of Cu-MOF-74 to the PEO-based electrolyte (15%Cu-MOF/P-Li) effectively improves the ionic conductivity, lithium transference number, and mechanical strength of the PEO-based electrolyte simultaneously. Furthermore, the ordered pore channels of Cu-MOF-74 provide uniform Li-ion transport pathways, facilitating homogeneous Li+ deposition. As a result, the lithium symmetric cell with 15%Cu-MOF/P-Li shows stable cycles for 1080 h at 0.1 mA cm-2 and 0.1 mAh cm-2, and the Li | 15% Cu-MOF/P-Li | LFP full cell exhibits a long cycle life up to 200 cycles at 60 °C and 0.5 C, with a capacity retention rate of 89.7%.

Outcomes for nighttime bracing in adolescent idiopathic scoliosis based on brace wear adherence.

BACKGROUND: This study determined brace wear adherence for patients treated with nighttime braces and evaluated the effect of brace adherence on curve progression. METHODS: One hundred twenty-two patients with AIS ages 10-16 years, Risser stages 0-2, major curves 20°-40° treated with Providence nighttime braces prescribed to be worn at least 8 h per night were prospectively enrolled and followed until skeletal maturity or surgery. Brace adherence was measured using iButton temperature sensors after 3 months of brace initiation and at brace discharge. RESULTS: Curve types were single thoracolumbar/lumbar (62%, n = 76), double (36%, n = 44), and single thoracic (2%, n = 2). Brace adherence averaged 7.8 ± 2.3 h after 3 months (98% adherence) and 6.7 ± 2.6 h at brace discharge (84% adherence). Curves that progressed ≥ 6° had decreased brace adherence than non-progressive curves after 3 months (7.0 h vs. 8.1 h, p = 0.010) and at brace discharge (5.9 h vs. 7.1 h, p = 0.017). Multivariate logistic regression analysis showed that increased hours of brace wear [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.06-1.46], single curves (OR 3.11, 95% CI 1.35-7.53), and curves < 25° (OR 2.61, 95% CI 1.12-6.44) were associated with non-progression at brace discharge. CONCLUSIONS: Patients treated with nighttime bracing have a high rate of brace adherence. Lack of curve progression is associated with increased brace wear. Nighttime bracing is effective at limiting curve progression in AIS single thoracolumbar/lumbar and double curves. LEVEL OF EVIDENCE: Prognostic Level 2.

Traditional knowledge of animal-derived medicines used by Gelao community in Northern Guizhou, China.

INTRODUCTION: This study aims to document and preserve the traditional medicinal knowledge of the Gelao community in Northern Guizhou, China, providing valuable insights for modern pharmacological research and the development of these traditional remedies. METHODS: Our methodology encompassed a blend of literature review, community interviews, and participatory observation to delve into the traditional knowledge of animal-derived medicines among the Gelao community. We employed quantitative ethnological and ecological assessment techniques to evaluate the significance of these practices. Informed consent was secured before conducting interviews, with a focus on ascertaining the types of medicines familiar to the informants, including their local names, sources, methods of preparation, application techniques, diseases treated, frequency of use, and safety considerations. RESULTS: Our research cataloged 55 varieties of animal-derived medicines utilized by the Gelao people. Out of these, 34 originate from wild animals, mainly encompassing small insects, reptiles, and aquatic species; the remaining 21 are derived from domesticated animals, largely involving their tissues, organs, and various physiological or pathological by-products. These medicines are primarily applied in treating pediatric ailments (13 types), internal disorders (11 types), gynecological issues (3 types), dermatological problems (7 types), ENT conditions (3 types), trauma-related injuries (5 types), joint and bone ailments (5 types), infections (2 types), dental issues (2 types), and urolithiasis (1 type), with three types being used for other miscellaneous conditions. Commonly utilized medicines, such as honey, Blaps beetle, chicken gallstones, and snake-based products, are preferred for their availability, edibility, and safety within the Gelao communities. CONCLUSION: The Gelao community's traditional medicines represent a rich diversity of animal sources, showcasing extensive expertise and knowledge in their processing and clinical applications. This wealth of traditional knowledge offers novel perspectives for the contemporary pharmacological study and development of these remedies. Additionally, our research plays a crucial role in aiding the preservation and continuation of this invaluable cultural heritage.

Exposure to different surface-modified polystyrene nanoparticles caused anxiety, depression, and social deficit in mice via damaging mitochondria in neurons.

Nanoplastics (NPs) are unavoidable hazardous materials that result from the human production and use of plastics. While there is evidence that NPs can bioaccumulate in the brain, no enough research regarding the pathways by which NPs reach the brain was conducted, and it is also urgently needed to evaluate the health threat to the nervous system. Here, we observed accumulation of polystyrene nanoplastics (PS-NPs) with different surface modifications (PS, PS-COOH, and PS-NH2) in mouse brains. Further studies showed that PS-NPs disrupted the tight junctions between endothelial cells and transport into endothelial cells via the endocytosis and macropinocytosis pathways. Additionally, NPs exposure induced a series of alternations in behavioral tests, including anxiety- and depression-like changes and impaired social interaction performance. Further results identified that NPs could be internalized into neurons and localized in the mitochondria, bringing about mitochondrial dysfunction and a concurrent decline of ATP production, which might be associated with abnormal animal behaviors. The findings provide novel insights into the neurotoxicity of NPs and provide a basis for the formulation of policy on plastic production and usage by relevant government agencies.

Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, significantly contributes to cancer-related mortality, presenting a dearth of efficacious treatment strategies. Previously, our studies have substantiated the potent cytotoxicity of arsenic trioxide (ATO) against NB cells, however, the specific underlying mechanism remains elusive. Here, we first identified ATO as a novel GPX4 inhibitor, which could trigger the ferroptosis in NB cells. In vitro, ATO significantly inhibited the proliferation and migration ability of NB cells SK-N-AS and SH-SY5Y, and induced ferroptosis. Furthermore, the iron chelator deferoxamine reversed ATO-mediated intracellular reactive oxygen species accumulation and hindered the generation of the lipid peroxidation product malondialdehyde. Conversely, ferric ammonium citrate notably intensified its cytotoxic effects, especially on retinoic acid (RA)-resistant SK-N-AS cells. Subsequently, the quantitative real-time polymerase chain reaction results showed ATO significantly inhibited the transcription of GPX4 in NB cells. Remarkably, immunoblotting analysis revealed that MG132 exhibited a notable effect on elevating GPX4 levels in NB cells. Nevertheless, pretreatment with MG132 failed to reverse the ATO-mediated decrease in GPX4 levels. These findings suggested that ATO reduced the GPX4 expression level in NB cells by mediating GPX4 transcriptional repression rather than facilitating ubiquitinated degradation. In conclusion, our research has successfully indicated that ATO could induce ferroptosis and initiate lipid peroxidation by regulating the transcriptional repression of GPX4, and ATO holds promise as a potential anti-tumor agent in NB, specifically for patients with RA-resistant HR-NB.

Relationship between hyperuricemia and the risk of cardiovascular events and chronic kidney disease in both the general population and hypertensive patients: A systematic review and meta-analysis.

BACKGROUND: To explore the relationships between hyperuricemia and the risk of cardiovascular diseases (CVD) and chronic kidney disease (CKD) in both the general population and hypertensive patients through meta-analysis. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane Library databases from January 2012. The eligibility criteria were predefined, and quality was assessed using the Newcastle-Ottawa Scale (NOS). Stata 15.1 was used for meta-analysis, heterogeneity and sensitivity analysis. Subgroup analysis was used to explore heterogeneity, funnel plots and Egger tests were used to assesse publication bias and applicability. A total of 10,662 studies were retrieved, 45 of which were included in this meta-analysis utilizing a random effects model. Hyperuricemia was significantly associated with an increased risk of new-onset hypertension (RR = 1.36, 95% CI 1.16-1.59; I2 = 98.8%), total CVD (RR = 1.53, 95% CI 1.23-1.89; I2 = 93.7%), stroke (RR = 1.97, 95% CI 1.71-2.26, I2 = 0.0%), coronary heart disease (CHD) (RR = 1.56, 95% CI 1.06-2.30, I2 = 93.3%), and CKD (RR = 1.71, 95% CI 1.56-1.87; I2 = 87.3%). However, subgroup analysis showed no significant associations between hyperuricemia and hypertension in non-Asian populations (RR = 0.88, 95% CI 0.59-1.33), or between hyperuricemia and CVD with a follow-up duration <5 years (RR = 1.26, 95% CI 0.97-1.63). Among hypertensive patients, hyperuricemia was significantly associated with total CVD (RR = 2.32, 95% CI 1.31-4.12, I2 = 90.2%), but not with stroke (RR = 1.48, 95% CI 0.86-2.55; I2 = 90.7%) or CHD (RR = 1.51, 95% CI 0.98-2.33; I2 = 71.7%). CONCLUSION: Hyperuricemia was significantly associated with an increased risk of new-onset hypertension, total CVD, stroke, CHD, and CKD in the general population. Among hypertensive patients, hyperuricemia was associated with an increased risk of CVD but not stroke or CHD alone. REGISTRATION NUMBER: CRD42022370692.

The prognostic significance of POD24 in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.

Alleviation of salinity stress by EDTA chelated-biochar and arbuscular mycorrhizal fungi on maize via modulation of antioxidants activity and biochemical attributes.

Salinity stress adversely affects agricultural productivity by disrupting water uptake, causing nutrient imbalances, and leading to ion toxicity. Excessive salts in the soil hinder crops root growth and damage cellular functions, reducing photosynthetic capacity and inducing oxidative stress. Stomatal closure further limits carbon dioxide uptake that negatively impact plant growth. To ensure sustainable agriculture in salt-affected regions, it is essential to implement strategies like using biofertilizers (e.g. arbuscular mycorrhizae fungi = AMF) and activated carbon biochar. Both amendments can potentially mitigate the salinity stress by regulating antioxidants, gas exchange attributes and chlorophyll contents. The current study aims to explore the effect of EDTA-chelated biochar (ECB) with and without AMF on maize growth under salinity stress. Five levels of ECB (0, 0.2, 0.4, 0.6 and 0.8%) were applied, with and without AMF. Results showed that 0.8ECB + AMF caused significant enhancement in shoot length (~ 22%), shoot fresh weight (~ 15%), shoot dry weight (~ 51%), root length (~ 46%), root fresh weight (~ 26%), root dry weight (~ 27%) over the control (NoAMF + 0ECB). A significant enhancement in chlorophyll a, chlorophyll b and total chlorophyll content, photosynthetic rate, transpiration rate and stomatal conductance was also observed in the condition 0.8ECB + AMF relative to control (NoAMF + 0ECB), further supporting the efficacy of such a combined treatment. Our results suggest that adding 0.8% ECB in soil with AMF inoculation on maize seeds can enhance maize production in saline soils, possibly via improvement in antioxidant activity, chlorophyll contents, gas exchange and morphological attributes.

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAFV600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation. METHODS: In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH. RESULTS: Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAFV600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2. CONCLUSION: Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.

The Synthesis of Three-Dimensional Hexagonal Boron Nitride as the Reinforcing Phase of Polymer-Based Electrolyte for All-Solid-State Li Metal Batteries.

Powdery hexagonal boron nitride (h-BN), as an important material for electrochemical energy storage, has been typically synthesized in bulk and one/two-dimensional (1/2D) nanostructured morphologies. However, until now, no method has been developed to synthesize powdery three-dimensional (3D) h-BN. This work introduces a novel NaCl-glucose-assisted strategy to synthesize micron-sized 3D h-BN with a honeycomb-like structure and its proposed formation mechanism. We propose that NaCl acts as the template of 3D structure and promotes the nitridation reaction by adsorbing NH3 . Glucose facilitates the homogeneous coating of boric acid onto the NaCl surface via functionalizing the NaCl surface. During the nitridation reaction, boron oxides (BO4 and BO3 ) form from a dehydration reaction of boric acid, which is then reduced to O2 -B-N and O-B-N2 intermediates before finally being reduced to BN3 by NH3 . When incorporated into polyethylene oxide-based electrolytes for Li metal batteries, 5 wt % of 3D h-BN significantly enhances ionic conductivity and mechanical strength. Consequently, this composite electrolyte demonstrates superior electrochemical stability. It delivers 300 h of stable cycles in the Li//Li cell at 0.1 mA cm-2 and retains 89 % of discharge capacity (138.9 mAh g-1 ) after 100 cycles at 1 C in the LFP//Li full cell.

The treatment outcomes of cracked teeth: A systematic review and meta-analysis.

OBJECTIVES: The aim of this review was to analyze the clinical treatment outcomes of cracked teeth (CT) retaining vital dental pulp (CT-VDP) or undergoing root canal treatment (CT-RCT). SOURCES: A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. STUDY SELECTION: Studies evaluating tooth survival rate (TSR), pulp survival rate (PSR), and success rate (SR) with at least a one-year follow-up were included. The risk of bias was evaluated with the Newcastle-Ottawa scale. DATA: Twenty-seven studies underwent qualitative analysis, 26 of which were included in the meta-analysis. SR of monitoring without restorative treatments was 80 % at three years. TSR of CT-VDP was 92.8-97.8 % at 1‒6 years, PSR of CT-VDP was 85.6‒90.4 % at 1‒3 years, and SR of CT-VDP was 80.6‒89.9 % at 1‒3 years; TSR of CT-RCT was 90.5‒91.1 % at 1‒2 years, and SR of CT-RCT was 83.0‒91.2 % at 1‒4 years. Direct restorations without cuspal coverage for CT-VDP increased the risk ratio (RR) of pulpal complications (RR=3.2, 95 % CI: 1.51-6.82, p = 0.002) and tooth extraction (RR=8.1, 95 % CI: 1.05-62.5, p = 0.045) compared with full-crown restorations. The CT-RCT without full-crown restorations had an 11.3-fold higher risk of tooth extraction than the CT-RCT with full-crown restorations (p < 0.001). CONCLUSIONS: Monitoring without restorative treatments might be an option for the CT without any symptoms. Direct restorations without cuspal coverage for the CT-VDP could significantly increase the RR of pulpal complications and tooth extraction compared with full-crown restorations. Full-crown restorations are strongly recommended for the CT-RCT. CLINICAL SIGNIFICANCE: Monitoring without restorative treatments could be a viable option for the CT without any symptoms. Full-crown restorations are strongly recommended for the CT with any symptoms and the CT-RCT.

Back pain and disability according to early onset scoliosis etiology in children younger than 10 years.

PURPOSE: To determine caregiver-reported back pain prevalence, disability, pain interference, and associations with curve magnitude in early onset scoliosis (EOS) using the Oswestry Disability Index (ODI) and Patient Reported Outcome Measurement Information Systems (PROMIS) measures. METHODS: A single-center, retrospective review was performed in children below 10 years of age according to EOS etiology. Caregiver-reported back pain prevalence, ODI, PROMIS Pain Interference, Mobility, and Anxiety measures, and curve magnitude were recorded as part of routine clinic appointments. RESULTS: A total of 1212 patients with EOS (588 idiopathic, 295 congenital, 217 neuromuscular, 112 syndromic) ages 6.6 ± 2.7 were included; 23% had caregiver-reported back pain. Neuromuscular EOS patients had the highest prevalence of back pain (29%). ODI scores were higher in neuromuscular (48%) and syndromic (35%) patients than congenital (20%, p < 0.05) and idiopathic (16%, p < 0.01) patients. Neuromuscular patients also had higher PROMIS Pain Interference scores (53.3) compared to idiopathic (41.6, p < 0.001) and syndromic (45.0, p = 0.016) patients. A higher curve was associated with the presence of back pain (39° vs. 30°, p < 0.001) and had positive correlations with ODI scores (r = 0.38, p < 0.001) and PROMIS Pain Interference scores (r = 0.34, p < 0.001). CONCLUSION: Approximately one in five children with EOS under the age of 10 have caregiver-reported back pain, with the neuromuscular EOS type exhibiting higher pain prevalence, interference, and disability scores. Larger curve magnitude is associated with an increased prevalence of caregiver-reported back pain, increased disability, and increased pain interference. LEVEL OF EVIDENCE: 3 - case-control study.

Mediation of association between semen microcystin exposure and semen quality by sex hormones in Chinese men.

Numerous studies have shown microcystins (MCs) inducing male reproductive toxicity, but the underlying mechanisms in humans are unclear. Therefore, this study aimed to evaluate the mediating role of serum sex hormones in the association between MC exposure and semen quality. In this study, we measured the levels of semen MCs and serum sex hormones in Chinese men [sample 1 (n = 649); sample 2 (n = 924)]. The results showed that there was a non-significant dose-dependent relationship between semen MCs and semen volume reduction (p for trend = 0.079) in sample 1, and semen MCs were significantly negatively associated with total motility, progressive motility, curvilinear velocity, mean angular displacement and acrosome integrity (p < 0.05) in sample 2. We also found that semen MCs were significantly positively associated with serum follicle stimulating hormone (FSH) (ß = 0.151; 95% CI: 0.065, 0.236), but negatively associated with serum inhibin B (INHB) (ß = -0.605; 95% CI: -0.944, -0.265), and these linear associations were confirmed in restricted cubic spline (RCS) models (all pnon-linearity > 0.1). Furthermore, mediation analysis revealed that serum INHB mediated 19.86% of the adverse effect of MC exposure on acrosome integrity. In conclusion, this study reveals the mediating roles of serum sex hormones in the relationship between MC exposure and decreased semen quality in men.

γ-Aminobutyric acid (GABA) and ectoine (ECT) impacts with and without AMF on antioxidants, gas exchange attributes and nutrients of cotton cultivated in salt affected soil.

Salinity stress is one of the major hurdles in agriculture which adversely affects crop production. It can cause osmotic imbalance, ion toxicity that disrupts essential nutrient balance, impaired nutrient uptake, stunted growth, increased oxidative stress, altered metabolism, and diminished crop yield and quality. However, foliar application of osmoprotectant is becoming popular to resolve this issue in crops. These osmoprotectants regulate the cellular osmotic balance and protect plants from the detrimental effects of high salt concentrations. Furthermore, the role of arbuscular mycorrhizae (AMF) is also established in this regard. These AMF effectively reduce the salinity negative effects by improving the essential nutrient balance via the promotion of root growth. That's why keeping in mind the effectiveness of osmoprotectants current study was conducted on cotton. Total of six levels of γ-Aminobutyric acid (GABA = 0 mM, 0. 5 mM, and 1 mM) and ectoine (ECT = 0 mM, 0.25 mM, and 0.5 mM) were applied as treatments in 3 replications. Results showed that 0.5 mM γ-Aminobutyric acid and ectoine performed significantly best for the improvement in cotton growth attributes. It also caused significant enhancement in K and Ca contents of the leaf, stem, bur, and seeds compared to the control. Furthermore, 0.5 mM γ-Aminobutyric acid and ectoine also caused a significant decline in Cl and Na contents of leaf, stem, bur, and seeds of cotton compared to control under salinity stress. A significant enhancement in chlorophyll contents, gas exchange attributes, and decline in electrolyte leakage validated the effectiveness of 0.5 mM γ-Aminobutyric acid and ectoine over control. In conclusion, 0.5 mM γ-Aminobutyric acid and ectoine have the potential to mitigate the salinity stress in cotton.

Arsenic Trioxide inhibits Activation of Hedgehog Pathway in Human Neuroblastoma Cell Line SK-N-BE(2) Independent of Itraconazole.

BACKGROUND: Neuroblastoma (NB) remains associated with a low overall survival rate over the long term. Abnormal activation of the Hedgehog (HH) signaling pathway can activate the transcription of various downstream target genes that promote NB. Both arsenic trioxide (ATO) and itraconazole (ITRA) can inhibit tumor growth. OBJECTIVE: To determine whether ATO combined with ITRA can be used to treat NB with HH pathway activation, we examined the effects of ATO and ITRA monotherapy or combined inhibition of the HH pathway in NB. METHODS: Analysis of CCK8 and flow cytometry showed cell inhibition and cell cycle, respectively. Real-time PCR analysis was conducted to assess the mRNA expression of HH pathway. RESULTS: We revealed that as concentrations of ATO and ITRA increased, the killing effects of both agents on SK-N-BE(2) cells became more apparent. During G2/M, the cell cycle was largely arrested by ATO alone and combined with ITRA, and in the G0/G1 phase by ITRA alone. In the HH pathway, ATO inhibited the transcription of the SHH, PTCH1, SMO and GLI2 genes, however, ITRA did not. Instead of showing synergistic effects in a combined mode, ITRA decreased ATO inhibitory effects. CONCLUSION: We showed that ATO is an important inhibitor of HH pathway but ITRA can weaken the inhibitory effect of ATO. This study provides an experimental evidence for the clinical use of ATO and ITRA in the treatment of NB with HH pathway activation in cytology.

Chidamide Induces Epstein-Barr Virus (EBV) Lytic Infection and Acts Synergistically with Tenofovir to Eliminate EBV-Positive Burkitt Lymphoma.

Epstein-Barr virus (EBV) is a type of human γ-herpesvirus, and its reactivation plays an important role in the development of EBV-driven Burkitt lymphoma (BL). Despite intensive chemotherapy, the prognosis of relapsed/refractory BL patients remains unfavorable, and a definitive method to completely eliminate latent EBV infection is lacking. Previous studies have demonstrated that histone deacetylase (HDAC) inhibitors can induce the transition of EBV from latency to the lytic phase. The lytic activation of EBV can be inhibited by tenofovir, a potent inhibitor of DNA replication. Herein, we explored the antitumor effect and EBV clearance potential of a novel HDAC inhibitor called chidamide, combined with tenofovir, in the treatment of EBV-positive BL. In the study, chidamide exhibited inhibitory activity against HDAC. Moreover, chidamide inhibited BL cell proliferation, arrested cell cycle progression, and induced BL cell apoptosis primarily by regulating the MAPK pathways. Additionally, chidamide promoted the transcription of lytic genes, including BZLF1, BMRF1, and BMLF1 Compared with chidamide alone, the addition of tenofovir further induced growth arrest and apoptosis in EBV-positive BL cells and inhibited the transcriptions of EBV lytic genes induced by chidamide alone. Furthermore, our in vivo data demonstrated that the combination of chidamide and tenofovir had superior tumor-suppressive effects in a mouse model of BL cell tumors. The aforementioned findings confirm the synergistic effect of chidamide combined with tenofovir in inducing growth inhibition and apoptosis in EBV-positive BL cells and provide an effective strategy for eliminating EBV and EBV-associated malignancies. SIGNIFICANCE STATEMENT: High levels of Epstein-Barr virus (EBV)-DNA have consistently been associated with unfavorable progression-free survival and overall survival in EBV-associated lymphomas. Therefore, identifying novel strategies to effectively eradicate tumor cells and eliminate EBV is crucial for lymphoma patients. This study confirmed, for the first time, the synergistic effect of chidamide combined with tenofovir in the treatment of Burkitt lymphoma and the eradication of EBV virus.