Qizhu anticancer prescription enhances immunosurveillance of liver cancer cells by regulating p21-dependent secretory phenotypes.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, largely due to the limitations of available therapeutic strategies. The traditional Chinese medicine Qizhu Anticancer Prescription (QZACP) can improve the quality of life and prolong the survival time of patients with HCC. However, the precise mechanisms underlying the anti-cancer properties of QZACP remain unclear. PURPOSE: This study examined the anti-hepatocarcinogenic properties of QZACP, with a specific focus on its influence on the p21-activated secretory phenotype (PASP)-mediated immune surveillance, to elucidate the underlying molecular pathways involved in HCC. MATERIALS AND METHODS: Cell proliferation was measured using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and clonogenic assays. The cell cycle was evaluated using flow cytometry, and senescence was identified by staining with senescence-associated beta-galactosidase (SA-ß-gal). A primary liver cancer model produced by diethylnitrosamine was established in C57 BL/6 mice to assess the tumor-inhibitory effect of QZACP. The liver's pathological characteristics were examined using hematoxylin and eosin staining. PASP screening was performed using GeneCards, DisGeNet, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas databases. Western blot analysis, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and Transwell migration assays were performed. RESULTS: Serum containing QZACP enhanced p21 expression, triggered cell cycle arrest, accelerated cell senescence, and suppressed cell proliferation in Huh7 and MHCC-97H liver cancer cells. QZACP reduced the quantity and dimensions of liver tumor nodules and enhanced p21 protein expression, SA-ß-Gal staining in tumor lesions, and cytotoxic CD8+ T cell infiltration. Bioinformatic analyses indicated that PASP factors, including hepatocyte growth factor, decorin (DCN), dermatopontin, C-X-C motif chemokine ligand 14 (CXCL14), and Wnt family member 2 (WNT2), play an important role in the development of HCC. In addition, these factors are associated with the presence of natural killer cells and CD8+ T cells within tumors. Western blotting and ELISA confirmed that QZACP increased DCN, CXCL14, and WNT2 levels in tumor tissues and peripheral blood. CONCLUSIONS: QZACP's suppression of HCC progression may involve cell senescence mediated via p21 upregulation, DCN, CXCL14, and WNT2 secretion, and reversal of the immunosuppressive microenvironment. This study provides insights that can be used in the development of new treatment strategies for HCC.

An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.

Revealing the intrinsic relationship between microbial communities and physicochemical properties during ripening of Xuanwei ham.

To clarify the relationship between microorganisms and physicochemical indicators of Xuanwei ham. Six ham samples for the first, second and third year were selected, respectively. The changes of physicochemical properties, the free fatty acids and microbial communities of Xuanwei ham were investigated by GC-MS and high-throughput sequencing technology. Results showed that scores of colour, overall acceptability, texture, taste and aroma were the highest in the third year sample. With increasing ripening time, moisture content, water activity (Aw), lightness (L*), springiness, and resilience decreased continuously, and yellowness (b*) was the highest in the second year sample. 31 free fatty acids were detected, and unsaturated fatty acids such as palmitoleic acid, oleic acid, and linoleic acid were the major fatty acids. The content of palmitoleic acid, oleic acid and eicosenoic acid increased significantly during processing. At the phylum level, the dominant bacteria were Proteobacteria and Firmicutes, and fungi were Ascomycota. At the genus level, the dominant bacteria were Staphylococcus and Psychrobacter, and fungi were Aspergillus. Correlation analysis showed that water content and Aw were closely related to microorganisms, and most unsaturated fatty acids were significantly correlated with microorganisms. These findings showed that microorganisms played an important role in the quality of Xuanwei ham, and provided a scientific basis for the quality control of Xuanwei ham.

Enhancement of ZT in Bi0.5Sb1.5Te3 Thin Film through Lattice Orientation Management.

Thermoelectric power can convert heat and electricity directly and reversibly. Low-dimensional thermoelectric materials, particularly thin films, have been considered a breakthrough for separating electronic and thermal transport relationships. In this study, a series of Bi0.5Sb1.5Te3 thin films with thicknesses of 0.125, 0.25, 0.5, and 1 µm have been fabricated by RF sputtering for the study of thickness effects on thermoelectric properties. We demonstrated that microstructure (texture) changes highly correlate with the growth thickness in the films, and equilibrium annealing significantly improves the thermoelectric performance, resulting in a remarkable enhancement in the thermoelectric performance. Consequently, the 0.5 µm thin films achieve an exceptional power factor of 18.1 µWcm-1K-2 at 400 K. Furthermore, we utilize a novel method that involves exfoliating a nanosized film and cutting with a focused ion beam, enabling precise in-plane thermal conductivity measurements through the 3ω method. We obtain the in-plane thermal conductivity as low as 0.3 Wm-1K-1, leading to a maximum ZT of 1.86, nearing room temperature. Our results provide significant insights into advanced thin-film thermoelectric design and fabrication, boosting high-performance systems.

Effects of repetitive transcranial magnetic stimulation on fear of cancer recurrence and its underlying neuromechanism.

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment. Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated. Ethics and dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. Trial registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.

Interceed combined with bone marrow mesenchymal stem cells improves endometrial receptivity of intrauterine adhesion.

Background: This study aimed to investigate the impact of intrauterine adhesions (IUA) therapy and endometrial receptivity by implanting autologous bone marrow mesenchymal stem cells (BMSCs) into the Interceed and subsequently placing them in the uterine cavity of rats. Methods: Fifty rats were divided into 5 groups according to the random number table method (10 rats in each group). Following the development of the IUA model through mechanical injury, the animals were categorized into different treatment groups: the IUA model (intrauterine perfusion of saline), Interceed therapy (intrauterine placement of Interceed), BMSCs therapy (intrauterine perfusion of BMSCs), BMSCs + Interceed therapy (intrauterine placement of BMSCs + Interceed), and a control group (intrauterine perfusion of saline). The Hematoxylin-eosin (HE) staining technique was employed to identify and assess the pathological alterations in the endometrium. Additionally, it facilitated the quantification of endometrial glands and the determination of endometrial thickness. Masson staining was used to detect fibrosis in rat uterus. The number of microvascular density (MVD) was detected by immunohistochemistry (IHC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the levels of leukemia inhibitory factor (LIF), integrin ανß3, and vascular endothelial growth factor (VEGF) in uterine tissue. Male and female rats were combined in cages for reproductive and conception evaluation. Results: In comparison to the control, the number of endometrial glands in the IUA model was significantly reduced, and the degree of endometrial thinning and fibrosis was significantly increased (p < 0.05). Compared with the IUA model, the number of endometrial glands did not exhibit any significant alterations in endometrial thickness and MVD number. The expressions of LIF, integrin ανß3, and VEGF in the uterine tissue were not significantly improved with Interceed therapy, resulting in no significant improvement in the pregnancy rate (p > 0.05). The number of endometrial glands, endometrial thickness, and MVD in the BMSCs therapy group were significantly increased. Moreover, the expressions of LIF, integrin ανß3, and VEGF in uterine tissue exhibited a significant increase, leading to a comparatively higher pregnancy rate (p < 0.05). In the BMSCs + Interceed therapy group, the number of endometrial glands, endometrial thickness, and MVD were significantly increased, and the expressions of LIF, integrin ανß3, and VEGF in uterine tissue were significantly increased as well, along with a corresponding rise in the pregnancy rate (p < 0.05). Conclusion: The intrauterine placement of Interceed combined with BMSCs in IUA rats can thicken the damaged endometrium, increase the number of glands, promote endometrial angiogenesis, improve endometrial receptivity, and increase the rate of pregnancy in IUA rats.

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly.

INTRODUCTION: Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia. METHODS: We enrolled volunteer the elderly subjects. Subjects were classified as dementia group and non-dementia group by instrument of ascertainment of dementia 8. All were assigned to attend 3 hours of MNPI (physical fitness training, Chinese capillary, and Chinese drawings and paintings) twice a week over a 16-week period. Neuropsychiatric tests, including Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI), were administered before and 1 year after MNPI. We demonstrated the changes of cognition and behavioral and psychological symptoms of dementia (BPSD) before and after MNPI. We compared the different effectiveness of cognition preservation between two groups. RESULTS: In total, there were 43 participants in our study, including 18 with non-dementia and 25 with dementia. The non-dementia group had a significantly higher proportion of cognitive preservation in remote memory (100.0% vs 68.0%, P = .007), orientation (94.4% vs 48.0%, P = .001), drawing (94.4% vs 64.0%, P = .021) and language (77.8% vs 48.0%, P = .049) than the dementia group. The highest proportion of preserved cognition after MNPI was remote memory (100%), followed by orientation (94.4%) and drawing (94.4%) in the non-dementia group. The highest proportion of preserved cognition after MNPI was attention (72%) followed by remote memory (68%), recent memory (64%) and drawing (64%) in the dementia group. Overall, their improved rate in behavioral and psychological symptoms was 55.6%. CONCLUSION: Our study concluded the benefits of early MNPI in cognition preservation in the elderly, especially in the field of remote memory, orientation, drawing and language.

Recent advances on environmental behavior of Cu-based nanomaterials in soil-plant system: A review.

In recent years, copper-based nanomaterials (Cu-based NMs) have shown great potential in promoting agriculture development due to their special physicochemical characteristics. With the mass production and overuse of Cu-based NMs, there are potential effects on the soil-plant environment. Soil organisms, especially soil microorganisms, play a significant part in terrestrial or soil ecosystems; plants, as indirect organisms with soil-related Cu-based NMs, may affect human health through plant agricultural products. Understanding the accumulation and transformation of Cu-based NMs in soil-plant systems, as well as their ecotoxicological effects and potential mechanisms, is a prerequisite for the scientific assessment of environmental risks and safe application. Therefore, based on the current literature, this review: (i) introduces the accumulation and transformation behaviors of Cu-based NMs in soil and plant systems; (ii) focuses on the ecotoxicological effects of Cu-based NMs on a variety of organisms (microorganisms, invertebrates, and plants); (iii) reveals their corresponding toxicity mechanisms. It appears from studies hitherto made that both Cu-based NMs and released Cu2+ may be the main reasons for toxicity. When Cu-based NMs enter the soil-plant environment, their intrinsic physicochemical properties, along with various environmental factors, could also affect their transport, transformation, and biotoxicity. Therefore, we should push for intensifying the multi-approach research that focuses on the behaviors of Cu-based NMs in terrestrial exposure environments, and mitigates their toxicity to ensure the promotion of Cu-based NMs.

A review of SaiLuoTong (MLC-SLT) development in vascular cognitive impairment and dementia.

The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups.

Enantioselective remote methylene C-H (hetero)arylation of cycloalkane carboxylic acids.

Stereoselective construction of γ- and δ-stereocenters in carbonyl compounds is a pivotal objective in asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote γ-C-H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes γ-tertiary and α-quaternary stereocenters simultaneously in up to >99% enantiomeric excess, providing access to a wide range of cyclic chiral synthons and bioactive molecules. The sequential enantioselective editing of two methylene C-H bonds can be achieved by using chiral ligands with opposite configuration to construct carbocycles containing three chiral centers. Enantioselective remote δ-C-H (hetero)arylation is also realized to establish δ-stereocenters that are particularly challenging to access using classical methodologies.

Cracking the code of the cardiovascular enigma: hPSC-derived endothelial cells unveil the secrets of endothelial dysfunction.

Endothelial dysfunction is a central contributor to the development of most cardiovascular diseases and is characterised by the reduced synthesis or bioavailability of the vasodilator nitric oxide together with other abnormalities such as inflammation, senescence, and oxidative stress. The use of patient-specific and genome-edited human pluripotent stem cell-derived endothelial cells (hPSC-ECs) has shed novel insights into the role of endothelial dysfunction in cardiovascular diseases with strong genetic components such as genetic cardiomyopathies and pulmonary arterial hypertension. However, their utility in studying complex multifactorial diseases such as atherosclerosis, metabolic syndrome and heart failure poses notable challenges. In this review, we provide an overview of the different methods used to generate and characterise hPSC-ECs before comprehensively assessing their effectiveness in cardiovascular disease modelling and high-throughput drug screening. Furthermore, we explore current obstacles that will need to be overcome to unleash the full potential of hPSC-ECs in facilitating patient-specific precision medicine. Addressing these challenges holds great promise in advancing our understanding of intricate cardiovascular diseases and in tailoring personalised therapeutic strategies.

Diterpenoids from Acanthopanacis Cortex and their anti-inflammatory activity studies.

Acanthopanacis Cortex (A.-C) with a long history of more than1000 years, has been used to treat rheumatism effectively. Nineteen diterpenoids have been isolated from A.-C, including six new compounds (1-6). Among them, compounds 7, 9-11, 13, and 17 were discovered from A.-C for the first time. The structures of 1-6 were determined by analyzing their NMR data and comparing their experimental and calculated electronic circular dichroism spectra. Moreover, the single-crystal X-ray diffraction data of 1, 2, 8, and 14 were provided. The anti-inflammatory activity of 1-5 and 7-18 on neutrophil elastase, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) has been studied in vitro, and the results showed that 15 had almost no inhibitory effects on COX-1 at 200 µM but a significant activity against COX-2 with an IC50 of 0.73 ± 0.006 µΜ. It indicated that compound 15 can provide valuable information for the design of selective COX-2 inhibitors.

Peripheral inflammation and trajectories of depressive symptomology after ischemic stroke: A prospective cohort study.

BACKGROUND: Understanding the association of peripheral inflammation and post-stroke depressive symptomology (PSDS) might provide further insights into the complex etiological mechanism of organic depression. However, studies focusing on the longitudinal patterns of PSDS were limited and it remained unclear whether peripheral inflammation influences the occurrence and development of PSDS. METHODS: A total of 427 prospectively enrolled and followed ischemic stroke patients were included in the analytical sample. Depressive symptomology was assessed on four occasions during 1 year after ischemic stroke. Peripheral inflammatory proteins on admission and repeated measures of peripheral immune markers in three stages were collected. Latent class growth analysis (LCGA) was employed to delineate group-based trajectories of peripheral immune markers and PSDS. Multinomial regression was performed to investigate the association of peripheral inflammation with PSDS trajectories. RESULTS: Four distinct trajectories of PSDS were identified: stable-low (n = 237, 55.5 %), high-remitting (n = 120, 28.1 %), late-onset (n = 44, 10.3 %), and high-persistent (n = 26, 6.1 %) PSDS trajectories. The elevation of peripheral fibrinogen on admission increased the risk of high-persistent PSDS in patients with early high PSDS. Additionally, chronic elevation of innate immune levels might not only increase the risk of high-persistent PSDS in patients with early high PSDS but also increase the risk of late-onset PSDS in patients without early high PSDS. The elevation of adaptive immune levels in the convalescence of ischemic stroke may contribute to the remission of early high PSDS. CONCLUSIONS: Peripheral immunity could influence the development of PSDS, and this influence might have temporal heterogeneity. These results might provide vital clues for the inflammation hypothesis of PSD.

Impaired distal renal potassium handling in streptozotocin-induced diabetic mice.

Diabetes is closely associated with K+ disturbances during disease progression and treatment. However, it remains unclear whether K+ imbalance occurs in diabetes with normal kidney function. In this study, we examined the effects of dietary K+ intake on systemic K+ balance and renal K+ handling in streptozotocin (STZ)-induced diabetic mice. The control and STZ mice were fed low or high K+ diet for 7 days to investigate the role of dietary K+ intake in renal K+ excretion and K+ homeostasis, and to explore the underlying mechanism by evaluating K+ secretion-related transport proteins in distal nephrons. K+-deficient diet caused excessive urinary K+ loss, decreased daily K+ balance, and led to severe hypokalemia in STZ mice compared to control mice. In contrast, STZ mice showed an increased daily K+ balance and elevated plasma K+ level under K+-loading conditions. Dysregulation of the NaCl cotransporter (NCC), epithelia Na+ channel (ENaC), and renal outer medullary K+ channel (ROMK) was observed in diabetic mice fed either low or high K+ diet. Moreover, amiloride treatment reduced urinary K+ excretion and corrected hypokalemia in K+-restricted STZ mice. On the other hand, inhibition of SGLT2 by dapagliflozin promoted urinary K+ excretion and normalized plasma K+ level in K+-supplemented STZ mice, at least partly by increasing ENaC activity. We conclude that STZ mice exhibited abnormal K+ balance and impaired renal K+ handling under either low or high K+ diet, which could be primarily attributed to the dysfunction of ENaC-dependent renal K+ excretion pathway, despite the possible role of NCC.

Defective natriuresis contributes to hyperkalemia in db/db mice during potassium supplementation.

OBJECTIVES: Potassium supplementation reduces blood pressure and the occurrence of cardiovascular diseases, with K+-induced natriuresis playing a potential key role in this process. However, whether these beneficial effects occur in diabetes remains unknown. METHODS: In this study, we examined the impact of high-K+ intake on renal Na+/K+ transport by determining the expression of major apical Na+ transporters, diuretics responses (as a proxy for specific Na+ transporter function), urinary Na+/K+ excretion, and plasma Na+/K+ concentrations in db/db mice, a model of type 2 diabetes mellitus. RESULTS: Although db/m mice exhibited increased fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) under high-K+ intake, these responses were largely blunted in db/db mice, suggesting impaired K+-induced natriuresis and kaliuresis in diabetes. Consequently, high-K+ intake increased plasma K+ levels in db/db mice, which could be attributed to the abnormal activity of sodium-hydrogen exchanger 3 (NHE3), sodium-chloride cotransporter (NCC), and epithelial Na+ channel (ENaC), as high-K+ intake could not effectively decrease NHE3 and NCC and increase ENaC expression and activity in the diabetic group. Inhibition of NCC by hydrochlorothiazide could correct the hyperkalemia in db/db mice fed a high-K+ diet, indicating a key role for NCC in K+-loaded diabetic mice. Treatment with metformin enhanced urinary Na+/K+ excretion and normalized plasma K+ levels in db/db mice with a high-K+ diet, at least partially, by suppressing NCC activity. CONCLUSION: Collectively, the impaired K+-induced natriuresis in diabetic mice under high-K+ intake may be primarily attributed to impaired NCC-mediated renal K+ excretion, despite the role of NHE3.

The impact of neurocognitive and psychiatric disorders on the risk of idiopathic normal pressure hydrocephalus: A bidirectional Mendelian randomization study.

BACKGROUND: Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis. METHODS: Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis. RESULTS: For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015). CONCLUSION: Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.

Anxiety and depression in nasopharyngeal carcinoma patients and network analysis to identify central symptoms: A cross-sectional study from a high-incidence area.

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.

PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice. Our results demonstrate that the acquired resistance to EGFR-TKIs is accompanied by aberrant expression of PD-L2, leading a dynamic shift from an initially favorable tumor immune environment to an immunosuppressive phenotype. PD-L2 expression significantly affected EGFR mutant cell apoptosis that depended on the proportion and function of CD8+ T cells in the tumor immune environment. Combined with single-cell sequencing and experimental results, we demonstrated that PD-L2 specifically inhibited the proliferation of CD8+ T cells and the secretion of granzyme B and perforin, leading to reduced apoptosis mediated by CD8+ T cells and enhanced immune escape of tumor cells, which drives EGFR-TKIs resistance. Importantly, we have identified a potent natural small-molecule inhibitor of PD-L2, zinc undecylenate. In vitro, it selectively and potently blocks the PD-L2/PD-1 interaction. In vivo, it abolishes the suppressive effect of the PD-L2-overexpressing tumor immune microenvironment by blocking PD-L2/PD-1 signaling. Moreover, the combination of zinc undecylenate and EGFR-TKIs can synergistically reverse tumor resistance, which is dependent on CD8+ T cells mediating apoptosis. Our study uncovers the PD-L2/PD-1 signaling pathway as a driving factor to mediate EGFR-TKIs resistance, and identifies a new naturally-derived agent to reverse EGFR-TKIs resistance.

The stratum corneum barrier: impaired function in relation to associated lipids and proteins.

The skin is the largest organ of the human body and is widely considered to be the first-line defense of the body, providing essential protection against mechanical, physical, and chemical damage. Keratinocytes are the primary cells of the outer layer of the epidermis, which acts as a mechanical and permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. Here we report that some components of keratinocytes affect the formation and differentiation of the stratum corneum, which is the most specialized layer of the epidermis.

[A comparative study of antioxidant active components in different parts of Artemisia argyi by UPLC-ABTS-Q-TOF-MS].

In order to characterize and identify the chemical components in different parts of Artemisia argyi(roots, stems, leaves, and seeds), compounds with antioxidant activity were screened. In this study, ultra-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt-quadrupole time-of-flight-tandem mass spectrometry(UPLC-ABTS-Q-TOF-MS) was used as an online combination technique. Poroshell 120 SB-Aq(3.0 mm×150 mm, 2.7 µm) was used as the column, and acetonitrile(A)-0.2% formic acid water(B) was adopted as the mobile phase to perform gradient elution and was scanned in positive and negative ion modes. MassLynx software was utilized, and combined with reference substances and related literature, the chemical components of different parts of A. argyi were identified and compared. The antioxidant active components were detected by using the online detection system, and the antioxidant activities of active components of different parts of A. argyi were compared and evaluated by scavenging efficiency. As a result, a total of 87 compounds were identified from extracts of different parts of A. argyi, and 38, 72, 85, and 33 components were identified from roots, stems, leaves, and seeds. 22 compounds with antioxidant activity were screened, and 14, 17, 20, and 11 compounds with antioxidant activity were identified from roots, stems, leaves, and seeds. The results show that there are certain differences in chemical components and antioxidant components of different parts of A. argyi, which provides data support for the resource utilization and further research and development of A. argyi.