Gut microbiota-astrocyte axis: new insights into age-related cognitive decline.

With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

[Distribution and health risk assessment of pesticide pollution in raw water and drinking water within key river basins in China in 2022].

OBJECTIVE: To investigate the distribution and exposure levels of pesticides in raw water and drinking water in China, as well as to assess the potential health risks associated with long-term consumption. METHODS: A total of 83 typical water plants were selected in key river basins in China to collected samples of the raw water, finished water, and tap water. The online-solid phase extraction coupled with liquid chromatography-tandem mass spectrometry method was used to determine 13 pesticides, including acetochlor, atrazine, dimethoate, malathion, carbofuran, dichlorvos, chlorpyrifos, parathion, trifluralin, isoprothiolane, simetryn, methyl parathion, and metalaxyl, as well as 6 environmental metabolites, including carbendazim, malaoxon, 3-hydroxycarbofuran, deethyl atrazine, deisopropyl atrazine and hydroxy atrazine. The carcinogenic and non-carcinogenic risks of these pesticides were assessed. RESULTS: The concentrations of total amount of pesticides in the samples ranged from 0.1 ng/L to 1299.4 ng/L, with a median value of 64.7 ng/L. The detection rates of 5 pesticides or their metabolites exceeds 80%, namely acetochlor, atrazine, hydroxyl atrazine, deethyl atrazine, and metalaxyl. More than 6 pesticides or their metabolites were detected in 77.7% of the total 498 samples. The total concentration of pesticides during the wet season ranged from 1.1 ng/L to 1299.4 ng/L, with a median of 69.2 ng/L and a median average daily dose of 2.3 ng/(kg·d). The total concentration of pesticides in the dry season samples ranged from 0.1 ng/L to 543.5 ng/L, with a median of 60.2 ng/L and a median average daily dose of 2.0 ng/(kg·d). Among the 498 samples, the maximum carcinogenic risk of dichlorvos was 2.0×10~(-7), and the maximum carcinogenic risk of trifluralin was 1.1×10~(-10). The non-carcinogenic HI of 19 pesticides and metabolites pesticides was ≤6.0×10~(-3). Among them, the maximum HI of the middle route of the South to North Water Diversion Project, the lower reaches of the Yellow River, the eastern route of the South to North Water Diversion Project, the Liaohe River, and the Songhua River basin was 2.0×10~(-3)-6.0×10~(-3), while the HI of other basins was less than 1.0×10~(-3). CONCLUSION: Different concentrations of pesticides have been detected in raw water, finished water, and tap water of key river basins in China, with the highest total concentration of detected reaching 1299.4 ng/L. The carcinogenic risk was lower than 10~(-6) and the non-carcinogenic hazard index of 19 pesticides was less than 1, and both below the acceptable level. Because of the universality and diverse occurrence of these pesticides in drinking water, long-term exposure to pesticides is still a concern.

Tibial transverse transport promotes wound healing in diabetic foot ulcers by stimulating endothelial progenitor cell mobilization and homing mediated neovascularization.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. METHODS: To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. RESULTS: TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

TTT accelerates wound healing in diabetic rabbit instep ulcers, with both unilateral and bilateral surgeries effective, and bilateral TTT showing enhanced efficacy.TTT boosts angiogenesis and collagen fiber formation, leading to increased granulation tissue and re-epithelialization of wounds.TTT induces the mobilization and homing of endothelial progenitor cells to promote angiogenesis and wound healing.

Added value of histogram analysis of intravoxel incoherent motion and diffusion kurtosis imaging for the evaluation of complete response to neoadjuvant therapy in locally advanced rectal cancer.

OBJECTIVE: To evaluate how intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis contribute to assessing complete response (CR) to neoadjuvant therapy (NAT) in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: In this prospective study, participants with LARC, who underwent NAT and subsequent surgery, with adequate MR image quality, were enrolled from November 2021 to March 2023. Conventional MRI (T2WI and DWI), IVIM, and DKI were performed before NAT (pre-NAT) and within two weeks before surgery (post-NAT). Image evaluation was independently performed by two experienced radiologists. Pathological complete response (pCR) was used as the reference standard. An IVIM-DKI-added model (a combination of IVIM and DKI histogram parameters with T2WI and DWI) was constructed. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of conventional MRI and the IVIM-DKI-added model. RESULTS: A total of 59 participants (median age: 58.00 years [IQR: 52.00, 62.00]; 38 [64%] men) were evaluated, including 21 pCR and 38 non-pCR cases. The histogram parameters of DKI, including skewness of kurtosis post-NAT (post-KSkewness) and root mean squared of change ratio of diffusivity (Δ%DDKI-root mean squared), were entered into the IVIM-DKI-added model. The area under the ROC curve (AUC) of the IVIM-DKI-added model for assessing CR to NAT was significantly higher than that of conventional MRI (0.855 [95% CI: 0.749-0.960] vs 0.685 [95% CI: 0.565-0.806], p < 0.001). CONCLUSION: IVIM and DKI provide added value in the evaluation of CR to NAT in LARC. KEY POINTS: Question The current conventional imaging evaluation system lacks adequacy for assessing CR to NAT in LARC. Findings Significantly improved diagnostic performance was observed with the histogram analysis of IVIM and DKI in conjunction with conventional MRI. Clinical relevance IVIM and DKI provide significant value in evaluating CR to NAT in LARC, which bears significant implications for reducing surgical complications and facilitating organ preservation.

Altered microbial diversity and composition of multiple mucosal organs in cervical cancer patients.

OBJECTIVES: The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients. METHODS: We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases. RESULTS: Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (pOral_Sob < 0.001, pOral_Shannon = 0.049, pOral_Simpson = 0.013 pFecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota (pVaginal_Pielou = 0.028, pVaginal_Simpson = 0.006). There were also significant differences in the ß-diversity of the microbiota at each site between cases and controls (pOral = 0.002, pFecal = 0.037, pUrine = 0.001, pVaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (pUrine = 0.036) and lymph node metastasis (pUrine_Sob = 0.027, pUrine_Pielou = 0.028, pUrine_Simpson = 0.021, pUrine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors. CONCLUSIONS: Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.

Spatial and temporal analysis and forecasting of TB reported incidence in western China.

OBJECTIVE: Tuberculosis (TB) remains an important public health concern in western China. This study aimed to explore and analyze the spatial and temporal distribution characteristics of TB reported incidence in 12 provinces and municipalities in western China and to construct the optimal models for prediction, which would provide a reference for the prevention and control of TB and the optimization of related health policies. METHODS: We collected monthly data on TB reported incidence in 12 provinces and municipalities in western China and used ArcGIS software to analyze the spatial and temporal distribution characteristics of TB reported incidence. We applied the seasonal index method for the seasonal analysis of TB reported incidence and then established the SARIMA and Holt-Winters models for TB reported incidence in 12 provinces and municipalities in western China. RESULTS: The reported incidence of TB in 12 provinces and municipalities in western China showed apparent spatial clustering characteristics, and Moran's I was greater than 0 (p < 0.05) over 8 years during the reporting period. Among them, Tibet was the hotspot for TB incidence in 12 provinces and municipalities in western China. The reported incidence of TB in 12 provinces and municipalities in western China from 2004 to 2018 showed clear seasonal characteristics, with seasonal indices greater than 100% in both the first and second quarters. The optimal models constructed for TB reported incidence in 12 provinces and municipalities in western China all passed white noise test (p > 0.05). CONCLUSIONS: As a hotspot of reported TB incidence, Tibet should continue to strengthen government leadership and policy support, explore TB intervention strategies and causes. The optimal prediction models we developed for reported TB incidence in 12 provinces and municipalities in western China were different.

Co-Infection of Bertiella studeri and Mycobacterium tuberculosis in a Captive Rhesus Macaque (Macaca mulatta).

Bertiella studeri, a typical intestinal cestode of nonhuman primates, accidentally infects human beings. However, B. studeri infection in monkeys has been rarely reported in recent years. A case of B. studeri infection was identified in one captive rhesus macaque with natural infection of Mycobacterium tuberculosis. This study contributes to alerting the public of this helmintic zoonosis, though its infection rate is quite lower in recent years.

[Spatiotemporal Differentiation of Carbon Emissions from Logistics Industry at Provincial Scale in China Under the Background of High-quality Economic Development].

Since 2010, the Chinese economy has transitioned from a high-speed growth model to a high-quality development model. During this period, the logistics industry has witnessed rapid growth, leading to significant carbon emissions and posing severe threats to the ecological environment. To investigate the spatiotemporal variations in carbon emissions in China's logistics industry, we conducted a correlation analysis using Moran's I index and a bivariate spatial autocorrelation model from 2010 to 2021. Additionally, we employed a geographically and temporally weighted regression model （GTWR） to examine the spatial heterogeneity of factors influencing provincial-level logistics-related carbon emissions. The results indicated that over the study period, there was a shift from insignificant spatial relationships to significant positive spatial correlations among provincial-level logistics carbon emissions in China. Furthermore, varying degrees of spatial clustering were observed. The findings regarding factor heterogeneity revealed that freight turnover volume, per capita GDP of the logistics industry, and infrastructure level exhibited positive spatial correlations with logistics-related carbon emissions, whereas energy intensity showed negative spatial correlations with such emissions. Comparing the results from the geographically weighted regression （GWR） and ordinary least squares regression （OLS）, it was evident that the adjusted R-squared values for the OLS, GWR, and GTWR models were 0.541, 0.567, and 0.838, respectively. This suggests that our adopted GTWR model provided a superior fit and offered better explanations for spatiotemporal heterogeneity between various influencing factors and logistics-related carbon emissions. These research findings can serve as valuable references for formulating province-specific strategies to reduce carbon emissions within China's economy under its high-quality development context.

Phase I clinical trial of NH130 and the prediction of its pharmacokinetics using physiologically based pharmacokinetic modeling.

Background: Parkinson's disease psychosis (PDP) is a common and distressing complication of Parkinson's disease (PD), characterized by hallucinations and delusions. This research aimed to assess the pharmacokinetics and safety of NH130, a selective serotonin 5-HT2A inverse agonist, as a potential PDP treatment in healthy individuals. Methods: We conducted clinical pharmacokinetic studies and safety evaluations for NH130, employing a physiologically based pharmacokinetic (PBPK) model to predict its behavior in human body. Results: In a single-dose escalation study, healthy volunteers received NH130 at varying doses (2 mg, 6 mg, 12 mg, 24 mg, 40 mg, 60 mg, and 90 mg) or a placebo. The drug demonstrated favorable pharmacokinetics, with no serious adverse events (AEs) reported. Clinical plasma concentrations correlated well with PBPK model predictions, validating the model's utility for guiding future clinical development. Conclusion: NH130 showed promising pharmacokinetic characteristics and safety profile, supporting its progression to multi-dose trials and suggesting its potential as a therapeutic agent for PDP. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, Identifier CTR20230409.

Biotoxicity of silver nanoparticles complicated by the co-existence of micro-/nano-plastics.

Silver nanoparticles (AgNP) and polystyrene (PS) plastics have been broadly utilized in various field, e.g., food storage, packaging materials, and medical therapies. However, investigation on the potential biotoxicity induced by the co-exposure to AgNP and PS plastics remains understudied. Thus, we performed this study to examine the toxicological profile of the co-exposure to AgNP and PS in mice. Biochemical and microbial characterizations were performed in mice receiving 90-day oral gavage feeding to examine the hepatotoxicity, neurotoxicity, inflammatory responses, gut microbial alterations. It has been found that the presence of plastic particles aggravates the toxicity of silver nanoparticle materials. Regardless of the plastic type and size, energy and choline metabolisms will be altered by the co-exposures. Moreover, microplastics may induce cell damage by modulating fatty acid peroxidation in unison with stimulating inflammatory responses. Due to the smaller size of nanoplastics, they may pass through blood-brain barrier to induce neuronal damage and increase vascular risks. Changes in the microbial functional abundances are sensitive to the microplastics doses. These results support the necessity of reducing the co-exposure between AgNP and multiscale plastics, and advocate further developments of biodegradable package materials to improve food safety.

The downregulation of TREM2 exacerbates toxicity of development and neurobehavior induced by aluminum chloride and nano-alumina in adult zebrafish.

To investigate the difference in the development and neurobehavior between aluminum chloride (AlCl3) and nano-alumina (AlNPs) in adult zebrafish and the role of triggering receptor expressed on myeloid cells (TREM2) in this process. Zebrafish embryos were randomly administered with control, negative control, TREM2 knockdown, AlCl3, TREM2 knockdown + AlCl3, AlNPs, and TREM2 knockdown + AlNPs, wherein AlCl3 and AlNPs were 50 mg/L and TREM2 knockdown was achieved by microinjecting lentiviral-containing TREM2 inhibitors into the yolk sac. We assessed development, neurobehavior, histopathology, ultrastructural structure, neurotransmitters (AChE, DA), SOD, genes of TREM2 and neurodevelopment (α1-tubulin, syn2a, mbp), and AD-related proteins and genes. AlCl3 significantly lowered the malformation rate than AlNPs, and further increased rates of malformation and mortality following TREM2 knockdown. The locomotor ability, learning and memory were similar between AlCl3 and AlNPs. TREM2 deficiency further exacerbated their impairment in panic reflex, microglia decrease, and nerve fibers thickening and tangling. AlCl3, rather than AlNPs, significantly elevated AChE activity and p-tau content while decreasing TREM2 and syn2a levels than the control. TREM2 loss further aggravated impairment in the AChE and SOD activity, and psen1 and p-tau levels. Therefore, AlCl3 induces greater developmental toxicity but equivalent neurobehavior toxicity than AlNPs, while their toxicity was intensified by TREM2 deficiency.

Virus-like Particles vaccine based on co-expression of G5 Porcine rotavirus VP2-VP6-VP7 induces a powerful immune protective response in mice.

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65 nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40 µg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

Unraveling the multifaceted role of SIRT7 and its therapeutic potential in human diseases.

Sirtuins, as NAD+-dependent deacetylases, are widely found in eubacteria, archaea, and eukaryotes, and they play key roles in regulating cellular functions. Among these, SIRT7 stands out as a member discovered relatively late and studied less extensively. It is localized within the nucleus and displays enzymatic activity as an NAD+-dependent deacetylase, targeting a diverse array of acyl groups. The role of SIRT7 in important cellular processes like gene transcription, cellular metabolism, cellular stress responses, and DNA damage repair has been documented in a number of studies conducted recently. These studies have also highlighted SIRT7's strong correlation with human diseases like aging, cancer, neurological disorders, and cardiovascular diseases. In addition, a variety of inhibitors against SIRT7 have been reported, indicating that targeting SIRT7 may be a promising strategy for inhibiting tumor growth. The purpose of this review is to thoroughly look into the structure and function of SIRT7 and to explore its potential value in clinical applications, offering an essential reference for research in related domains.

Analysis of turnover intention and influencing factors among female nurses with two children in Grade A tertiary public hospitals in Sichuan province: a cross-sectional study.

Objective: This study aims to examine the current status of turnover intention among female nurses with two children and explore the factors influencing their decision to resign, ultimately providing a basis for reducing nurses' turnover intention and stabilizing the nursing workforce. Methods: A convenience sampling method was used to select 1,370 in-service female nurses with two children from 65 Grade A tertiary public hospitals in Sichuan Province from September to December 2023. Data was collected through a general information questionnaire, work-family behavioral role conflict scale, regulatory emotional self-efficacy, and turnover intention scale. Results: This study revealed that the average score for turnover intention among female nurses with two children was (13.11 ± 3.93). There was a positive correlation between work-family behavioral role conflict and turnover intention (r = 0.485, p < 0.01), while regulatory emotional self-efficacy showed a negative correlation with turnover intention (r = -0.382, p < 0.01). The main influencing factors for resignation among these nurses included age, number of night shifts per month, average monthly income, primary caregiver for children, work-to-family conflict and family-to-work conflict, and the ability to express positive emotions (POS), the capacity to regulate negative emotions such as despondency/distress (DES), and the skill to manage anger/irritation (ANG). Collectively, these factors explained 29.5% of the total variance in turnover intention scores. Conclusion: Turnover intention among female nurses with two children is relatively high. To address this issue, hospital managers shall implement effective measures through various channels to settle work-family conflict, enhance nurses' regulatory emotional self-efficacy, and reduce turnover intention resulting from work-family conflict. Together, these efforts will reduce nurse turnover and foster a stable nursing workforce.

Toxicity of gold nanoparticles complicated by the co-existence multiscale plastics.

Introduction: Gold nanoparticles (AuNPs) have been developed as treatment materials for various diseases and shown magnificent potential. By contrast to the broad toxicological studies on the single exposure (AuNPs), how the other health risks modulate the toxicological profile of AuNPs remains to be investigated. Plastics are among the most common health risks in daily life due to the broad utilization of plastic products. Therefore, in this study, we aimed to reveal the toxicological effects induced by co-exposure of gold nanorod (AuR) and polystyrene micro- and nano-plastics (hereinafter, referred to as AuRmPS and AuRnPS, respectively) in mice. Methods: Systematic biochemical characterizations were performed to investigate the hepatotoxicity, nephrotoxicity, neurotoxicity, inflammatory responses, alterations in gut microbiota induced by co-exposure, and to analyze the toxicological phenomena from the roles of reactive oxygen species and gut-organ axis. Results: It has been found that hepatotoxicity, nephrotoxicity, neurotoxicity, and inflammation were exacerbated in AuRnPS and AuRmPS, and gut microbiota composition was more severely altered in AuRnPS exposure. These results suggest the necessity of reducing plastics exposure in AuNPs-based therapies. Moreover, protection against the nano-sized plastic particles holds higher priority. Conclusion: These findings will facilitate the explorations of methods to reduce therapeutic toxicity and improve biosafety for specific treatments by referring to the orders of importance in protecting different organs.

Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot.

OBJECTIVE: Continuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. METHODS: Clinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. RESULTS: The joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). CONCLUSION: The joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.

ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions.

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family.

The Complex FtBBX22 and FtHY5 Positively Regulates Light-Induced Anthocyanin Accumulation by Activating FtMYB42 in Tartary Buckwheat Sprouts.

Anthocyanin is one important nutrition composition in Tartary buckwheat (Fagopyrum tataricum) sprouts, a component missing in its seeds. Although anthocyanin biosynthesis requires light, the mechanism of light-induced anthocyanin accumulation in Tartary buckwheat is unclear. Here, comparative transcriptome analysis of Tartary buckwheat sprouts under light and dark treatments and biochemical approaches were performed to identify the roles of one B-box protein BBX22 and ELONGATED HYPOCOTYL 5 (HY5). The overexpression assay showed that FtHY5 and FtBBX22 could both promote anthocyanin synthesis in red-flower tobacco. Additionally, FtBBX22 associated with FtHY5 to form a complex that activates the transcription of MYB transcription factor genes FtMYB42 and FtDFR, leading to anthocyanin accumulation. These findings revealed the regulation mechanism of light-induced anthocyanin synthesis and provide excellent gene resources for breeding high-quality Tartary buckwheat.

Prebiotic stachyose inhibits PRDX5 activity and castration-resistant prostate cancer development.

Stachyose (STA) is a prebiotic with poor oral bioavailability. In this study, we developed stachyose caproate (C6-STA), as a novel STA derivative, to demonstrate its high adsorption rate via oral administration. Pharmacokinetic analysis reveals that after absorption, the STA derived from C6-STA reaches its highest peak in the blood, liver, and kidney at 20 min, 30 min, and 12-24 h, with approximate levels of 1200 µg/mL, 0.14 µg/mL, and 0.2-0.3 µg/mL, respectively. In addition, the accumulation of STA in prostate tissues of mice with castration-resistant prostate cancer (CRPC) (1.75 µg/mg) is 10-fold higher than that in normal prostate tissues (0.14 µg/mg). The analysis also reveals that C6-STA has t1/2 of 12.8 h and Tmax of 0.25 h, indicating that it has the potential to be used as a promising drug in clinical practice. The toxicological evaluation shows no obvious side effects of C6-STA in mice administered with a 0.2 g/kg intragastric dose. Pharmacodynamic analysis and mechanism investigation of C6-STA show its ability to inhibit peroxiredoxin 5 (PRDX5) enzyme activity, disrupt PRDX5-nuclear factor erythroid 2-related factor 2 (NRF2) interaction, and decrease NAD(P)H quinone dehydrogenase 1 (NQO1) levels. NQO1 decrease further causes the accumulation of quinone radicals, which ultimately leads to the apoptosis of LNCaP cell-derived drug-tolerant persister (DTP) cells and slows CRPC progression. Our study discovered the anti-tumor activity of stachyose and shows that prebiotics have biological functions in vivo besides in the gut. Further investigation of C6-STA, especially in CRPC patients, is warranted.