Development and validation of a lung cancer polygenic risk score incorporating susceptibility variants for risk factors.

Incorporating susceptibility genetic variants of risk factors has been reported to enhance the risk prediction of polygenic risk score (PRS). However, it remains unclear whether this approach is effective for lung cancer. Hence, we aimed to construct a meta polygenic risk score (metaPRS) of lung cancer and assess its prediction of lung cancer risk and implication for risk stratification. Here, a total of 2180 genetic variants were used to develop nine PRSs for lung cancer, three PRSs for different histopathologic subtypes, and 17 PRSs for lung cancer-related risk factors, respectively. These PRSs were then integrated into a metaPRS for lung cancer using the elastic-net Cox regression model in the UK Biobank (N = 442,508). Furthermore, the predictive effects of the metaPRS were assessed in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial (N = 108,665). The metaPRS was associated with lung cancer risk with a hazard ratio of 1.33 (95% confidence interval: 1.27-1.39) per standard deviation increased. The metaPRS showed the highest C-index (0.580) compared with the previous nine PRSs (C-index: 0.513-0.564) in PLCO. Besides, smokers in the intermediate risk group predicted by the clinical risk model (1.34%-1.51%) with the intermediate-high genetic risk had a 6-year average absolute lung cancer risk that exceeded the clinical risk model threshold (≥1.51%). The addition of metaPRS to the clinical risk model showed continuous net reclassification improvement (continuous NRI = 6.50%) in PLCO. These findings suggest the metaPRS can improve the predictive efficiency of lung cancer compared with the previous PRSs and refine risk stratification for lung cancer.

Family history and genetic risk score combined to guide cancer risk stratification: A prospective cohort study.

Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (Ptrend < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies.

Large and non-spherical seeds are less likely to form a persistent soil seed bank.

There is some evidence that seed traits can affect the long-term persistence of seeds in the soil. However, findings on this topic have differed between systems. Here, we brought together a worldwide database of seed persistence data for 1474 species to test the generality of seed mass-shape-persistence relationships. We found a significant trend for low seed persistence to be associated with larger and less spherical seeds. However, the relationship varied across different clades, growth forms and species ecological preferences. Specifically, relationships of seed mass-shape-persistence were more pronounced in Poales than in other order clades. Herbaceous species that tend to be found in sites with low soil sand content and precipitation have stronger relationships between seed shape and persistence than in sites with higher soil sand content and precipitation. For the woody plants, the relationship between persistence and seed morphology was stronger in sites with high soil sand content and low precipitation than in sites with low soil sand content and higher precipitation. Improving the ability to predict the soil seed bank formation process, including burial and persistence, could benefit the utilization of seed morphology-persistence relationships in management strategies for vegetation restoration and controlling species invasion across diverse vegetation types and environments.

The association between METS-IR, an indirect index for insulin resistance, and lung cancer risk.

BACKGROUND: Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. METHODS: A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. RESULTS: During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30-11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17-1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45-109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94-48.59) with low METS-IR and PRS. CONCLUSIONS: High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer.

Association between the prognostic nutritional index and severe headache or migraine: a population-based study.

PURPOSE: Migraine is a highly prevalent headache disorder, and intake of various nutrients and special diets may improve migraine symptoms. We aimed to clarify the association between nutritional status and migraine. PATIENTS AND METHODS: We collected the data of 1838/8953 (migraineurs/all participants) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 cycle. We used weighted multivariable linear or logistic regression analyses to study the association between the prognostic nutritional index (PNI) and the occurrence of severe headache or migraine. RESULTS: After adjusting for confounding variables, we found that mild (PNI 45-50) or moderate to severe (PNI <45) malnutrition were associated with higher prevalence of severe headache or migraine (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.12, P = 0.004; OR 1.07, 95% CI 1.03-1.12, P < 0.001). In addition, we found that those with severe headache or migraine consumed less alcohol, dietary fiber, cholesterol, total folate, vitamin A, riboflavin, vitamin B6, vitamin B12, vitamin C, vitamin K, selenium, potassium, magnesium, and copper, and consumed more caffeine and theobromine than did those without severe headache or migraine. CONCLUSION: The PNI is associated with migraine prevalence, and may thus serve as a predictor of migraine risk and highlights the potential of nutrition-based strategies for migraine prevention and treatment.

[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Evodiamine decreased the systemic exposure of pravastatin in non-alcoholic steatohepatitis rats due to the up-regulation of hepatic OATPs.

CONTEXT: Patients with non-alcoholic steatohepatitis (NASH) may have a simultaneous intake of pravastatin and evodiamine-containing herbs. OBJECTIVE: The effect of evodiamine on the pharmacokinetics of pravastatin and its potential mechanisms were investigated in NASH rats. MATERIALS AND METHODS: The NASH model was conducted with feeding a methionine choline-deficient (MCD) diet for 8 weeks. Sprague-Dawley rats were randomised equally (n = 6) into NASH group, evodiamine group (10 mg/kg), pravastatin group (10 mg/kg), and evodiamine (10 mg/kg) + pravastatin (10 mg/kg) group. Normal control rats were fed a standard diet. Effects of evodiamine on the pharmacokinetics, distribution, and uptake of pravastatin were investigated. RESULTS: Evodiamine decreased Cmax (159.43 ± 26.63 vs. 125.61 ± 22.17 µg/L), AUC0-t (18.17 ± 2.52 vs. 14.91 ± 2.03 mg/min/L) and AUC0-∞ (22.99 ± 2.62 vs. 19.50 ± 2.31 mg/min/L) of orally administered pravastatin in NASH rats, but had no significant effect in normal rats. Evodiamine enhanced the uptake (from 154.85 ± 23.17 to 198.48 ± 26.31 pmol/mg protein) and distribution (from 736.61 ± 108.07 to 911.89 ± 124.64 ng/g tissue) of pravastatin in NASH rat liver. The expression of Oatp1a1, Oatp1a4, and Oatp1b2 was up-regulated 1.48-, 1.38-, and 1.51-fold by evodiamine. Evodiamine decreased the levels of IL-1ß, IL-6, and TNF-α by 27.82%, 24.76%, and 29.72% in NASH rats, respectively. DISCUSSION AND CONCLUSIONS: Evodiamine decreased the systemic exposure of pravastatin by up-regulating the expression of OATPs. These results provide a reference for further validation of this interaction in humans.

Development and external validation of a nomogram for neurosyphilis diagnosis among non-HIV patients: a cross-sectional study.

BACKGROUND: The diagnosis of neurosyphilis is challenging due to the requirement of a lumbar puncture and cerebrospinal fluid (CSF) laboratory tests. Therefore, a convenient diagnostic nomogram for neurosyphilis is warranted. This study aimed to construct diagnostic models for diagnosing neurosyphilis. METHODS: This cross-sectional study included data of two patient cohorts from Western China Hospital of Sichuan University between September 2015 and April 2021 and Shangjin Hospital between September 2019 and April 2021 as the development cohort and the external validation cohort, respectively. A diagnostic model using logistic regression analysis was constructed to readily provide the probability of diagnosis at point of care and presented as a nomogram. The clinical usefulness of the diagnostic models was assessed using a receiver operating characteristic (ROC) and Harrell concordance (Harrell C) index for discrimination and calibration plots for accuracy, which adopted bootstrap resampling 500 times. RESULTS: One hundred forty-eight and 67 patients were included in the development and validation cohorts, respectively. Of those, 131 were diagnosed as having reactive neurosyphilis under the criteria of positive results in both CSF treponemal and non-treponemal tests. In the development cohort, male, psychiatric behaviour disorders, and serum toluidine red unheated serum test were selected as diagnostic indicators applying a stepwise procedure in multivariable logistic model. The model reached 80% specificity, 79% sensitivity, and 0·85 area under the curves (AUC) (95% confidence interval, 0·76-0·91). In the validation cohorts, the Harrell C index for the diagnostic possibility of reactive neurosyphilis was 0·71. CONCLUSIONS: A convenient model using gender, presence of psychiatric behaviour disorders, and serum TRUST titre was developed and validated to indicate diagnostic results in patients suspected of neurosyphilis. Checking the model value of factors on nomogram is a feasible way to assist clinicians and primary health servers in updating patients' medical charts and making a quantitatively informed decision on neurosyphilis diagnosis. TRIAL REGISTRATION: This research was retrospectively registered in the Ethics committee on biomedical research, West China Hospital of Sichuan University. The research registration and committee's reference number was 1163 in 2020 approval.

Rutaecarpine enhances the anti-diabetic activity and hepatic distribution of metformin via up-regulation of Oct1 in diabetic rats.

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.

The impact of COVID-19 pandemic on headache symptoms and drug withdrawal among patients with medication overuse headache: a cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) bring about a range of psychological distress and symptom deterioration to headache patients especially to some migraineurs. Compared to migraineurs or normal control, medication overuse headache (MOH) patients are more likely to experience a worse psychological distress and poorer outcome in non-COVID-19 time. However, in COVID-19 pandemic, whether MOH patients would have greater physical and mental symptom deterioration or worse relief of headache symptoms and medications overuse remained unclear. We aim to investigate the impact of COVID-19 on MOH patients to guide for a better management in this study. METHODS: We enrolled MOH patients who were diagnosed and treated at headache clinic of West China Hospital. Information of the pre-pandemic 3 months period and COVID-19 pandemic period was collected. Univariate and multivariate logistic regression were performed to identify independent factors associated with changes in headache symptoms and drug withdrawal. RESULTS: Seventy-eight MOH patients were enrolled into the study ultimately. In comparison to pre-pandemic period, fewer MOH patients reported decreased headache days, intensity and days with acute medications per month during the pandemic. Available access to regular prophylactic medications was significantly associated with a reduction of at least 50% in headache days and decrease in headache intensity per month with respective odds ratios of 39.19 (95% CI 3.75-409.15, P = 0.002) and 10.13 (95% CI 2.33-44.12, P = 0.002). Following abrupt withdrawal and high educational level were both significant factors in decreasing headache intensity. Male sex was significantly associated with decrease in days with acute medication per month during the pandemic (odds ratios 4.78, 95%CI 1.44-15.87, P = 0.011). CONCLUSIONS: Our findings reflect that MOH patients experienced a worse relief of headache symptoms and drug withdrawal during the pandemic. Available access to regular prophylactic medications was the significant independent factor for improvement of headache symptoms. Male sex was significantly associated with decreased days with acute medications per month.

An activating transcription factor 6 beta (ATF6ß) regulates apoptosis of hemocyte during immune response in Crassostrea gigas.

The homeostasis of immune cells during immune response is vital for hosts to defend against invaders. Activating transcription factor 6 (ATF6) is an important transcription factor in the unfolded protein response (UPR) to maintaining cellular homeostasis. In the present study, one ATF6 homologue was identified from Pacific oyster Crassostrea gigas (designated as CgATF6ß). The full length cDNA of CgATF6ß was of 2645 bp with a 1596 bp open reading frame (ORF) encoding a polypeptide of 531 amino acids. The deduced amino acid sequence of CgATF6ß was predicted to contain a transmembrane region, a conserved basic leucine zipper (bZIP) domain, a site 1 protease cleavage site, a site 2 protease cleavage site, and a Golgi localization signal. CgATF6ß mRNA was constitutively expressed in hemocytes, gill, mantle, gonad, hepatopancreas and labial palp, with a slightly higher expression level in muscle (2.45-fold of that in gill, p < 0.05). After oysters were challenged with Vibrio splendidus, the mRNA expression levels of CgATF6ß in hemocytes were significantly up-regulated at 3 h (2.68-fold of that in seawater group, p < 0.01) and peaked at 12 h (3.14-fold of that in seawater group, p < 0.01). The endogenic CgATF6ß protein was mainly located in the cytoplasm of oyster hemocytes, and it was significantly transported into the nuclei of hemocytes at 1.5 h after the challenge with V. splendidus. After an injection with CgATF6ß dsRNA, the mRNA expression of CgATF6ß was knocked down to 0.26-fold of that in dsGFP group (p < 0.01). In CgATF6ß dsRNA-injected oysters, the mRNA expressions of glucose-regulated protein 78 (GRP78), calnexin (CNX) and anti-apoptotic B-cell lymphoma-2 (Bcl-2) in hemocytes were significantly decreased at 12 h after V. splendidus challenge, which were 0.65-fold (p < 0.01), 0.54-fold (p < 0.01) and 0.17-fold (p < 0.01) of that in dsGFP-injected oysters, while the apoptotic rate of hemocytes was significantly up-regulated (1.97-fold of that in dsGFP group, p < 0.05). Collectively, these results suggested that CgATF6ß was involved in apoptosis inhibition of oyster hemocytes upon V. splendidus challenge by regulating the expression of CgGRP78, CgCNX and CgBcl-2.

Involvement of organic anion-transporting polypeptides and organic cation transporter in the hepatic uptake of jatrorrhizine.

Jatrorrhizine possesses a wide spectrum of pharmacological activities. However, the mechanism underlying hepatic uptake of jatrorrhizine remains unclear.Rat liver slices, isolated rat hepatocytes and human embryonic kidney 293 (HEK293) cells stably expressing human organic anion-transporting polypeptide (OATP) and organic cation transporter (OCT) were used to evaluate the hepatic uptake of jatrorrhizine in this study.Uptake of jatrorrhizine in rat liver slices and isolated rat hepatocytes was significantly inhibited by glycyrrhizic acid (Oatp1b2 inhibitor) and prazosin (Oct1 inhibitor), but not by ibuprofen (Oatp1a1 inhibitor) or digoxin (Oatp1a4 inhibitor). Uptake of jatrorrhizine in OATP1B3 and OCT1-HEK293 cells indicated a saturable process with the Km of 8.20 ± 1.28 and 4.94 ± 0.55 µM, respectively. However, the transcellular transport of jatrorrhizine in OATP1B1-HEK293 cells was not observed. Rifampicin (OATP inhibitor) for OATP1B3-HEK293 cells and prazosin for OCT1-HEK293 cells could inhibit the uptake of jatrorrhizine with the IC50 of 5.49 ± 1.05 and 2.77 ± 0.72 µM, respectively.The above data indicate that hepatic uptake of jatrorrhizine is involved in both OATP and OCT, which may have important roles in jatrorrhizine liver disposition and potential drug-drug interactions.

[Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats].

Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.

A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration.

AIMS: Variation in genes encoding GABAA receptor subunits has been implicated in the risk of alcohol dependence (AD). We sought to replicate and extend previous findings of a moderating effect of single nucleotide polymorphisms (SNPs) in GABRA2 (which encodes the GABAA α-2 subunit) on the subjective effects of alcohol by examining SNPs in this and the adjacent GABRG1 gene on chromosome 4. METHODS: Fifty-two European-Americans (22 males, 28 light drinkers and 24 heavy drinkers) completed 3 laboratory sessions, during which they drank low-dose, high-dose, or placebo alcohol prior to undergoing periodic assessments of stimulation, sedation and drug enjoyment. We genotyped subjects for three SNPs previously associated with AD: rs279858 in GABRA2, and rs7654165 and rs6447493 in GABRG1. RESULTS: Two SNPs were associated with altered stimulatory effects of alcohol as measured on the Biphasic Alcohol Effects Scale, (rs279858: P = 0.0046; rs6447493: P = 0.0023); both effects were in the opposite direction of previous findings. Carriers of the rs279858 C allele experienced greater stimulation from alcohol. Further inspection of the rs6447493 interaction did not support a pharmacogenetic effect. The effects of rs279858 (but not the other two SNPs) on items from a secondary outcome measure, the Drug Effects Questionnaire (DEQ), were significant. Higher ratings by individuals with the C allele were observed on the DEQ items 'feel the alcohol effect' (P < 0.001), 'like the alcohol effect' (P < 0.001) and feel 'high' (P < 0.001). CONCLUSION: We did not find that the GABRG1 SNPs rs7654165 and rs6447493 moderated the effects of alcohol. Greater stimulatory and euphoric effects of alcohol in carriers of the rs279858 C allele may, in part, explain the previously reported association of this allele with AD.

Right-sided infective endocarditis or thrombus? Report of two cases diagnosed by transthoracic echocardiography.

BACKGROUND: Right-sided infective endocarditis (RSIE) is a relatively uncommon condition which is difficult to distinguish from thrombus, particularly when the site of infection or the patient's symptoms are atypical. There have been few reports exploring the differential diagnostic and analytical features between RSIE and thrombus. CASE PRESENTATION: Here, we presented two cases of RSIE-one involving the tricuspid valve and the other affecting the pulmonary artery. Notably, the second case was initially misdiagnosed as thrombus based on the findings of by computed tomography angiography(CTA). CONCLUSIONS: Vegetation and thrombus can be distinguished according to the nature of the mass, its attachment location, and the clinical manifestation. Echocardiography can observe both the location and size of the mass, and the dynamic changes in cardiac hemodynamics and cardiac morphology, thereby facilitating an effective distinction between vegetation and thrombus.

Surface Engineering on Zinc Anode for Aqueous Zinc Metal Batteries.

Rechargeable aqueous zinc metal batteries (AZMBs) are considered as a potential alternative to lithium-ion batteries due to their low cost, high safety, and environmental friendliness. However, the Zn anodes in AZMBs face severe challenges, such as dendrite growth, metal corrosion, and hydrogen evolution, all of which are closely related to the Zn/electrolyte interface. This article offers a short review on surface passivation to alleviate the issues on the Zn anodes. The composition and structure of the surface layers significantly influence their functions and then the performance of the Zn anodes. The recent progresses are introduced, according to the chemical components of the passivation layers on the Zn anodes. Moreover, the challenges and prospects of surface passivation in stabilizing Zn anodes are discussed, providing valuable guidance for the development of AZMBs.

Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. RESULTS AND DISCUSSION: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. CONCLUSION: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Effect of copper and temperature on the photosynthetic physiological characteristics of Ulva linza under elevated CO2 concentrations.

Copper (Cu) is vital for macroalgae's functions, but high concentrations can be toxic. Rising CO2 levels affect algal growth and Cu bioavailability. In this study, the results reveal that at 5 °C, low Cu increased Ulva linza growth, while high Cu and elevated CO2 decreased growth. At 10 °C, low Cu and elevated CO2 enhanced growth, but high Cu did not have a significant impact. At 15 °C, high Cu reduced growth, but elevated CO2 offset this effect. Furthermore, under elevated CO2 conditions, the chloroplast structure of the algae appeared to be denser, accompanied by a large amount of starch granules, compared to low CO2 conditions. These results emphasize that lower temperatures, in conjunction with elevated CO2 concentration, could intensify the toxic effects of high Cu concentrations on thalli. However, at higher temperatures, elevated CO2 concentration appeared to be capable of mitigating the detrimental effects of heavy metals on algae.

Ocean acidification may alleviate the toxicity of zinc to the macroalga, Ulva lactuca.

We investigated the toxic effects of different zinc (Zn) concentrations (natural seawater, 25 µg/L, and 100 µg/L) under two CO2 concentrations (410 ppmv, and 1000 ppmv) on Ulva lactuca. A significant decrease in the relative growth rate of U. lactuca was observed with an increase in Zn concentration under the low CO2 treatment condition, and we observed a notable decrease at 100 µg/L Zn under the high CO2 treatment condition. Moreover, the net photosynthetic rate increased when thalli were cultured under 25 and 100 µg/L Zn under the high CO2 treatment condition. The concentrations of chlorophyll a and b were significantly increased under 100 µg/L Zn and the high CO2 treatment conditions. Malondialdehyde content decreased under high CO2 treatment conditions, compared with the low CO2 treatment conditions, regardless of the Zn concentration. These findings suggest that ocean acidification may alleviate the toxic effects of Zn pollution on U. lactuca.

Zn(002)-preferred and pH-buffering triethanolamine as electrolyte additive for dendrite-free Zn anodes.

Zn anodes of aqueous batteries face severe challenges from side reactions and dendrite growth. Here, triethanolamine (TEOA) is developed as an electrolyte additive to address these challenges. It enhances the exposure of Zn(002) and diminishes the change in pH. Therefore, the electrolyte containing TEOA shows improved electrochemical performance.