A fluorescent probe for monitoring carboxylesterases in pulmonary cells under permissive hypercapnia condition.

Herein, by combining the benzofuranone-derived fluorophore and the carbamate recognition group, a fluorescent probe named BFO-CarE was developed for monitoring the carboxylesterase (CarE) level in pulmonary cells under the permissive hypercapnia condition. It showed a notable fluorescence response towards CarE at 570 nm under the excitation of 510 nm. The in-solution tests revealed the advantages of BFO-CarE including high sensitivity, high specificity, relatively rapid response, and high steadiness. It was also low-toxic upon the pulmonary cell lines. During the intracellular imaging in pulmonary cells, BFO-CarE achieved the monitoring of the CarE level in both inhibition and activation status. In particular, BFO-CarE realized the visualization of the affection of the permissive hypercapnia condition on the CarE level, which indicated the hypoxia tolerance of CarE. This work was informative for investigating the impact of hypoxia in pulmonary cells, and the corresponding anaesthesia-related approaches.

Visual Analysis of Hot Topics and Trends in Nutrition for Decompensated Cirrhosis Between 1994 and 2024.

OBJECTIVE: An updated summary of the research profile of nutrition for the last 30 years for decompensated cirrhosis is lacking. This study aimed to explore the literature on nutrition for decompensated cirrhosis, draw a visual network map to investigate the research trends, and provide suggestions for future research. The Web of Science database retrieves the literature on nutrition for decompensated cirrhosis between 1994 and 2024. METHODS: We used the cooperative, co-occurrence, and co-citation networks in the CiteSpace knowledge graph analysis tool to explore and visualize the relevant countries, institutions, authors, co-cited journals, keywords, and co-cited references. RESULTS: We identified 741 articles on nutrition for decompensated cirrhosis. The number of publications and research interests has generally increased. The USA contributed the largest number of publications and had the highest centrality. The University of London ranked first in the number of articles issued, followed by the University of Alberta and Mayo Clinic. TANDON P, a "core strength" researcher, is a central hub in the collaborative network. Of the cited journals, HEPATOLOGY had the highest output (540, 15.3%). CONCLUSIONS: Over the past three decades, the focus of research on nutrition in decompensated cirrhosis has shifted from "hepatic encephalopathy, intestinal failure, metabolic syndrome, and alcoholic hepatitis" to "sarcopenia and nutritional assessment." In the future, nutritional interventions for sarcopenia should be based on a multimodal approach to address various causative factors. Its targeted treatment is an emerging area that warrants further in-depth research.

Stable Cu/Cu2O/CuN3@NC Catalysts for Aqueous Phase Reforming of Methanol.

Aqueous-phase reforming of methanol represents a promising avenue for hydrogen (H2) production. However, developing highly efficient and low-cost nonprecious catalysts remains challenging. Here, we report the synthesis of Cu-based catalysts with Cu, Cu2O, and CuN3 nanoparticles anchored on the nitrogen-doped carbon, forming Cu0/Cu+/Cu-N3 active sites. This catalyst achieves a H2 production rate of 140.1 µmol/gcat/s at 210 °C, which is several times to 2 orders of magnitude higher than that of Cu-, Ni-, even Pt-based catalysts, demonstrating excellent long-term stability over 350 h at 210 °C. A mechanism investigation reveals that the Cu-N3 site facilitates water dissociation into *OH and improves *CO and *OH conversion, leading to enhanced CO conversion and H2 production kinetics.

Taohong Siwu decoction enhances the chemotherapeutic efficacy of doxorubicin by promoting tumor vascular normalization.

BACKGROUND: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of "blood-activating and stasis-resolving" formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. PURPOSE: To study the underlying mechanisms of a classical "blood-activating and stasis-resolving" formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. STUDY DESIGN: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. RESULTS: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. CONCLUSION: This study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment.

Response surface methodology-based optimization of Inonotus hispidus' liquid fermentation medium and evaluation of its exopolysaccharide activities.

Introduction: Inonotus hispidus, commonly referred to as the Sanghuang mushroom, is a species that is consumed as a tea. To date, this is the only species of the same fungus that has been successfully cultivated. Methods: A single-factor test was conducted using Inonotus hispidus MS-5 and MS-9 as test materials. The response surface methodology was adopted to design and optimise the liquid fermentation medium for them. Results: As indicated in the results, the optimum fermentation conditions for MS-5 include 24.09 g/L glucose, 7.88 g/L yeast extract, 0.99 g/L dandelion powder, 1.5 g MgSO4, 2 g KH2PO4, 0.01 g vitamin B1, and 1 L deionized water; the optimum fermentation conditions for MS-9 include 24.64 g/L glucose, 7.77 g/L yeast extract, 0.98 g/L dandelion powder, 1.5 g MgSO4, 2 g KH2PO4, 0.01 g vitamin B1, and 1 L deionized water. Under such conditions, the mycelial biomass (dry weight) values were able to reach 16.02 g/L and 14.91 g/L for MS-5 and MS-9, respectively, which were 1.6 and 1.54 times those measured before optimization. Discussion: As revealed in the antioxidant and anticancer experiment, Inonotus hispidus exopolysaccharides has corresponding functional effects at the cellular level. This research optimised the liquid culture formulation of Inonotus hispidus and demonstrated that the function of it as a traditional Sanghuang herbal tea is well-documented.

Effect of the ten-year fishing ban on change of phytoplankton community structure: Insights from the Gan River.

The Yangtze River is one of the largest riverine ecosystems in the world and is a biodiversity hotspot. In recent years, this river ecosystem has undergone rapid habitat deterioration due to anthropogenic disturbances, leading to a decrease in freshwater biodiversity. Owing to these anthropogenic impacts, the Chinese government imposed a "Ten-year fishing ban" (TYFB) in the Yangtze River and its tributaries. Ecological changes associated with this decision have not been documented to evaluate the level of success. This study evaluates the success of the TYFB by analyzing the changes in phytoplankton communities and comparing them to periods before the TYFB was imposed. A total of 325 phytoplankton species belonging to 7 phyla and 103 genera dominated by Chlorophyceae and Bacillariophyceae were identified. Species diversity according to the Shannon-Wiener ranged between 1.19 and 3.00. The results indicated that phytoplankton diversity increased, while both density and biomass decreased after the TYFB. The health of the aquatic ecosystem appeared to have improved after the TYFB, as indicated by the phytoplankton-based index of biotic integrity. Significant seasonal and spatial differences were found among the number of species, density, and biomass of phytoplankton, where these differences were correlated with pH, water depth, chlorophyll-a, permanganate index, transparency, copper, ammonia nitrogen, and total phosphorus based on redundancy analysis. Results from this study indicate that the TYFB played an important role in the restoration of freshwater ecosystem in the Yangtze River and its tributaries.

Mesenchymal stem cell-derived extracellular vesicles mitigate neuronal damage from intracerebral hemorrhage by modulating ferroptosis.

BACKGROUND: Hemorrhagic stroke is a devastating cerebrovascular event with a high rate of early mortality and long-term disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, has garnered considerable interest, though their mechanisms of action remain poorly understood. METHODS: EVs were isolated from human umbilical cord MSCs, and SPECT/CT was used to track the 99mTc-labeled EVs in a mouse model of ICH. A series of comprehensive evaluations, including magnetic resonance imaging (MRI), histological study, RNA sequencing (RNA-Seq), or miRNA microarray, were performed to investigate the therapeutic action and mechanisms of MSC-EVs in both cellular and animal models of ICH. RESULTS: Our findings show that intravenous injection of MSC-EVs exhibits a marked affinity for the ICH-affected brain regions and cortical neurons. EV infusion alleviates the pathological changes observed in MRI due to ICH and reduces damage to ipsilateral cortical neurons. RNA-Seq analysis reveals that EV treatment modulates key pathways involved in the neuronal system and metal ion transport in mice subjected to ICH. These data were supported by the attenuation of neuronal ferroptosis in neurons treated with Hemin and in ICH mice following EV therapy. Additionally, miRNA microarray analysis depicted the EV-miRNAs targeting genes associated with ferroptosis, and miR-214-3p was identified as a regulator of neuronal ferroptosis in the ICH cellular model. CONCLUSIONS: MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders.

Dietary inflammatory index and its impact on severity and recurrence of Tourette syndrome in children.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and vocal tics, typically beginning in childhood. Despite significant research efforts, the exact pathophysiology of TS remains incompletely understood. Recent studies suggest that inflammation may play a role in the severity and progression of TS, pointing to the potential influence of dietary and lifestyle factors on the condition. Currently, research on the specific connection between dietary inflammatory index (DII) and TS is still in its early stages, requiring additional clinical and epidemiological studies to validate the strength and specific mechanisms of this connection. AIM: To investigate the association between DII and the severity, recurrence, and inflammatory levels of TS in children. METHODS: A total of 207 children diagnosed with TS in the pediatric department of Qingdao Chengyang People's Hospital from January 2022 to January 2023 were selected. They were divided into stable and unstable groups based on follow-up conditions. Before enrollment, general information of the children [age, gender, body mass index (BMI), guardian's education level, DII score, medical history, family history, academic stress, electronic device usage, medication, and disease progression] was assessed, and serum inflammatory levels were measured during follow-up visits. DII scores and Yale Global Tic Severity Scale (YGTSS) scores were calculated. Furthermore, based on YGTSS scores, the children were classified into mild, moderate, and severe groups. The DII, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels in each group were compared. RESULTS: Follow-up surveys were completed by 207 children and their guardians. Among them, 117 children were in the stable group, and 90 were in the recurrent group. We found no statistically significant differences in age, gender, comorbidities, BMI, and disease duration between the two groups (P > 0.05). However, academic stress, electronic device usage, medication, guardian's education level, and DII scores showed statistically significant differences between the groups (P < 0.05). Multifactorial regression analysis revealed that guardian's anxiety level, DII score, medication, academic stress, and family history were statistically significant factors (P < 0.05) affecting the recurrence of TS in children. Therefore, anxiety level, DII score, medication status, electronic device usage, and academic stress were identified as factors influencing the recurrence of TS in children. Among them, DII score, academic stress, and family history had odds ratios (OR) greater than 1, indicating risk factors, whereas medication status and guardian's education level had OR values less than 1, indicating protective factors. According to the YGTSS scores, children were categorized into mild, moderate, and severe groups. Comparative analysis of DII and inflammatory levels in children with different degrees of tic disorders revealed that the severe group had the highest DII and inflammatory levels, followed by the moderate group, and the mild group had the lowest levels. The trend of TS progression was consistent with the DII results. Receiver operating characteristic curves were plotted to predict disease progression in patients with TS via inflammatory markers. The areas under the curve for IL-6, CRP, and TNF-α were 0.894 (95%CI: 0.817-0.969), 0.793 (95%CI: 0.694-0.893), and 0.728 (95%CI: 0.614-0.843) respectively, with statistically significant differences (P < 0.05). According to the Youden index, the optimal cutoff values were IL-6 = 3.775 ng/L (sensitivity 68.1% and specificity 68.4%), CRP = 6.650 mg/L (sensitivity 60.6% and specificity 68.4%), and TNF-α = 0.666 (sensitivity 60.6% and specificity 71.1%). CONCLUSION: We found a certain correlation between DII and the severity, recurrence, and inflammatory levels of TS in children. Reasonable reduction in the intake of pro-inflammatory foods may be beneficial in reducing the risk of disease progression in children with TS.

Effects of the photovoltaic fishery culture model on muscle nutritional quality and volatile flavor compounds of Litopenaeus vannamei.

This study used Litopenaeus vannamei to compare the muscle nutritional quality and volatile flavor compounds of animals raised in the photovoltaic fishery culture model (PM) and the common pond breeding model (CM). Amino acids, fatty acids, and volatile flavor substances were identified and analyzed using an automatic amino acid analyzer and headspace solid phase microextraction(HS-SPME) combined with GC/MS. There were no significant differences between the two culture models in terms of general nutrients, mineral contents, and amino acid compositions in the muscles of L. vannamei. In the PM group, the proportion of flavor amino acids in total amino acids was higher. Based on the amino acid score (AAS) and chemical score (CS), it was found that methionine and cystine were the first limiting amino acids in the muscle samples. The essential amino acid index (EAAI) value was approximately 77 for both models, indicating high-quality proteins. The muscles contained nine types of fatty acids, with the PM group showing significantly higher levels of both monounsaturated and total fatty acids. A total of 23 volatile flavor compounds were identified in both models. The contents of 1-nonanal, n-tridecane, and alpha-terpineol were higher when cultured in the PM. Conversely, the contents of hexanal, 2-ethylhexanol, and dipentene were lower in the PM group. The photovoltaic fishery culture model has the potential to enhance income through photovoltaic power generation. In addition, this study found that the fatty acid composition of L. vannamei was improved in the PM, without compromising muscle composition or flavor. These results provide a theoretical basis for evaluating the meat quality of L. vannamei under different culture models and offer data to support and guide the promotion of the PM.

Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism.

Jaundice affects almost all neonates in their first days of life and is caused by the accumulation of bilirubin. Although the core biochemistry of bilirubin metabolism is well understood, it is not clear why some neonates experience more severe jaundice and require treatment with phototherapy. Here, we present the first genome-wide association study of neonatal jaundice to date in nearly 30,000 parent-offspring trios from Norway (cases ≈ 2000). The alternate allele of a common missense variant affecting the sequence of UGT1A4 reduces the susceptibility to jaundice five-fold, which replicated in separate cohorts of neonates of African American and European ancestries. eQTL colocalization analyses indicate that the association may be driven by regulation of UGT1A1 in the intestines, but not in the liver. Our results reveal marked differences in the genetic variants involved in neonatal jaundice compared to those regulating bilirubin levels in adults, suggesting distinct genetic mechanisms for the same biological pathways.

Bibliometrics and knowledge mapping of the pathogenesis of hepatic encephalopathy in patients with liver cirrhosis.

Background: Hepatic encephalopathy is a common and serious complication of decompensated cirrhosis. It can considerably contribute to economic burden and impaired quality of life. However, its pathogenesis remains unclear. Method: In this study, we aimed to visually analyse the research status and development trends in hepatic encephalopathy pathogenesis using bibliometrics and knowledge mapping. Information regarding publications between 1978 and 2022 were obtained from the Web of Science Core Collection. CiteSpace was used to analyse and present data by year, author, institution, country, journal, reference, and keyword. Results: A total of 1578 publications on hepatic encephalopathy pathogenesis in patients with cirrhosis were retrieved from Web of Science Core Collection. A gradual increasing trend in annual publications has occurred. The collaborative network analysis results suggest the United States of America, the University of London, and Bajaj, Jasmohan S as the most influential country, institution, and author, respectively, in this research field. Notably, China appeariiuis to be the most promising country. Research on 'hepatology' garners the most significant papers in the field. Combined with reference co-citation and keyword co-occurrence analyses, we found that ammonia metabolism, gut microbiota, sarcopenia, and trace elements will become future research frontiers that are likely to be explored for a considerable length of time. Conclusion: Future research directions in HE pathogenesis may target modulating the ammonia metabolism, the gut microbiota, sarcopenia, and trace elements.

PegIFN alpha-2a reduces relapse in HBeAg-negative patients after nucleo(s)tide analogue cessation: A randomized-controlled trial.

BACKGROUND & AIMS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse. However, the effect of pegylated interferon alpha-2a (PegIFN-α-2a) on virological relapse after NUC cessation is unknown. Therefore, this study aimed to evaluate the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96. METHODS: In this multicentre randomized controlled clinical trial, 180 non-cirrhotic HBeAg-negative chronic hepatitis B patients on continuous NUC therapy for ≥ 2.5 years with HBV DNA levels < 60 IU/mL were randomized to discontinue NUC (n=90) or receive 48 weeks of PegIFN-α-2a treatment (n=90) and followed up till 96 weeks. The primary endpoint was the virological relapse rate until week 96. RESULTS: Intention-to-treat analysis revealed patients in the interferon monotherapy group had significantly lower cumulative virological relapse rates than the NUC cessation group until week 96 (20.8% vs. 53.6%, P < 0.0001). Consistently, a significantly lower proportion of patients in the interferon monotherapy group had virological relapse than those in the NUC cessation group at 48 weeks off treatment (17.8% vs. 36.7%, P = 0.007). The virological relapse rate positively correlated with HBsAg levels in the NUC cessation group. The interferon monotherapy group had a lower cumulative clinical relapse rate (7.8% vs. 20.9%, P = 0.008) and a higher HBsAg loss rate (21.5% vs. 9.0%, P = 0.03) than the NUC cessation group. CONCLUSIONS: Switching from NUC to PegIFN-α-2a treatment for 48 weeks significantly reduces virological relapse rates and achieves higher HBsAg loss rates than NUC treatment cessation alone in HBeAg-negative chronic hepatitis B patients. IMPACT AND IMPLICATIONS: Nucleo(s)tide analogue (NUC) cessation can lead to HBsAg clearance but also a high rate of virological relapse, but an optimised scheme to reduce the virological relapse rate after NUC withdrawal is yet to be reported. This randomized controlled trial investigated the effect of switching from NUC to PegIFN-α-2a treatment for 48 weeks on virological relapse until week 96 in HBeAg-negative chronic hepatitis B patients. The interferon monotherapy group had a significantly lower cumulative virological relapse rate (20.8% vs. 53.6%, P < 0.0001) and higher HBsAg loss rate (21.5% vs. 9.0%, P= 0.03) than the NUC cessation group until week 96. This provides an optimized strategy for NUC cessation in HBeAg-negative patients. TRIAL REGISTRATION NUMBER: NCT02594293.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Cuproptosis related ceRNA axis AC008083.2/miR-142-3p promotes the malignant progression of nasopharyngeal carcinoma through STRN3.

Background: CeRNA axis is an important way to regulate the occurrence and development of Nasopharyngeal carcinoma (NPC). Although the research on inducing cuproptosis of tumor cells is in the early stage of clinical practice, its mechanism of action is still of great significance for tumor treatment, including NPC. However, the regulation mechanism of cuproptosis in NPC by ceRNA network remains unclear. Methods: The ceRNA network related to the survival of nasopharyngeal carcinoma related genes was constructed by bioinformatics. Dual-luciferase reporter assay and other experiments were used to prove the conclusion. Results: Our findings indicate that the AC008083.2/miR-142-3p axis drives STRN3 to promote the malignant progression of NPC. By performing enrichment analysis and phenotypic assays, we demonstrated that the changes in the expressions of AC008083.2/miR-142-3p/NPC can affect the proliferation of NPC. Mechanistically, luciferase reporter gene assays suggested that AC008083.2 acts as a ceRNA of miR-142-3p to regulate the content of STRN3. Furthermore, the regulations of STRN3 and the malignant progression of NPC by AC008083.2 depends on miR-142-3p to some extent. Conclusions: Our study reveals an innovative ceRNA regulatory network in NPC, which can be considered a new potential target for diagnosing and treating NPC.

Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage.

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal-fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.

Taxonomic revision of two species in the genus Ptychorhynchus Simpson, 1900 (Bivalvia: Unionidae: Gonideinae), with description of a new species.

Accurate identification and precise classification of freshwater mussel species that are among the most threatened freshwater taxa in the world, play a crucial role in informing conservation and management efforts for these organisms. However, due to the variability in shell morphology, relying solely on shell characteristics for species taxonomy poses significant challenges, thereby impeding effective conservation planning and management. The freshwater mussel genus Ptychorhynchus Simpson, 1900 is one such group in need of study. We integrate molecular phylogeny, shell morphology and soft-body anatomy to examine the classification of Ptychorhynchus denserugata (Haas, 1910) and Ptychorhynchus resupinatus (von Martens, 1902). The COI barcoding data support the clustering of P. denserugata and Nodularia douglasiae within a single clade, and P. denserugata shares the diagnostic feature of the genus Nodularia , i.e. knobs or bumps on the inner mantle surface in the excurrent aperture. Therefore, by integrating molecular data and anatomical characteristics, we confirm that the nominal species P. denserugata syn. nov. is a new synonym for N. douglasiae . The multi-locus (COI + ND1 + 16S rRNA + 18S rRNA + 28S rRNA ) phylogeny and mitochondrial phylogenomics support the transfer of P. resupinatus from Ptychorhynchus to the newly elevated genus Cosmopseudodon stat. rev., as Cosmopseudodon resupinatus stat. rev. that is still considered the designated type species. We also describe a new species based on integrative taxonomy, i.e. Cosmopseudodon wenshanensis sp. nov. The comprehensive understanding of the taxonomy and diversity of the revised Cosmopseudodon species, and shell heteromorphism of N. douglasiae (=P. denserugata syn. nov.), will serve as a crucial foundation for further scientific assessment and conservation strategies pertaining to these taxa. ZooBank: urn:lsid:zoobank.org:pub:E48968B1-DF0F-42AD-8F31-B8C95F23CE57.

Cordycepin Enhances the Therapeutic Efficacy of Doxorubicin in Treating Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. Meanwhile, doxorubicin, a chemotherapeutic agent for triple-negative breast cancer, has poor sensitivity. The objective of this study was to examine the effect of cordycepin on doxorubicin sensitivity and efficacy in the TNBC xenograft model and explore the relevant molecular pathways. The combination of the drugs in nude mice carrying MDA-MB-231 xenografts significantly reduced the volume, size, and weight of xenografts and improved the tumor inhibition rate. The drug combination was significantly more effective than cordycepin or doxorubicin alone, reflecting the fact that cordycepin enhanced the anti-tumor effects of doxorubicin in MDA-MB-231 xenografts. At the same time, the monitoring of several biological parameters failed to detect any obvious side effects associated with this treatment. After predicting the importance of the TNF pathway in inhibiting tumor growth using network pharmacology methods, we verified the expression of TNF pathway targets via immunohistochemistry and quantitative PCR. Furthermore, a TNF-α inhibitor was able to abrogate the beneficial effects of cordycepin and doxorubicin treatment in MDA-MB-231 cells. This clearly indicates the role of TNF-α, or related molecules, in mediating the therapeutic benefits of the combined treatment in animals carrying TNBC xenografts. The observations reported here may present a new direction for the clinical treatment of TNBC.

A new species of Pupinidius Möllendorff, 1901 (Gastropoda, Stylommatophora, Enidae) from Jiuzhaigou, Sichuan, China.

Background: The genus Pupinidius Möllendorff, 1901 is endemic in China and Nepal and consists of 15 species. China is the distribution centre of it with 12 species being recorded. New information: A new species, Pupinidiuspulchellus Chen, Dai, Wu & Ouyang sp. nov. is described from Jiuzhaigou, Sichuan, China. It can be distinguished from congeneric species by the shell with wide and distinct radial stripes; the thin, slightly reflexed and reddish-brown peristome; the unpointed apex; the unfused A-1 and A-2; the sub-globular and well defined bursa copulatrix; the unexpanded diverticle and the presence of epiphallic caecum.

Gray matter morphometric biomarkers for distinguishing manganese-exposed welders from healthy adults revealed by source-based morphometry.

BACKGROUND: Chronic overexposure to manganese (Mn) may result in neurotoxicity, which is characterized by motor and cognitive dysfunctions. This study aimed to utilize multivariate source-based morphometry (SBM) to explore the biomarkers for distinguishing Mn-exposed welders from healthy controls (HCs). METHODS: High-quality 3D T1-weighted MRI scans were obtained from 45 Mn-exposed full-time welders and 33 age-matched HCs in this study. After extracting gray matter structural covariation networks by SBM, multiple classic interaction linear models were applied to investigate distinct patterns in welders compared to HCs, and Z-transformed loading coefficients were compared between the two groups. A receiver operating characteristic (ROC) curve was used to identify potential biomarkers for distinguishing Mn-exposed welders from HCs. Additionally, we assessed the relationships between clinical features and gray matter volumes in the welders group. RESULTS: A total of 78 subjects (45 welders, mean age 46.23±4.93 years; 33 HCs, mean age 45.55±3.40 years) were evaluated. SBM identified five components that differed between the groups. These components displayed lower loading weights in the basal ganglia, thalamus, default mode network (including the lingual gyrus and precuneus), and temporal lobe network (including the temporal pole and parahippocampus), as well as higher loading weights in the sensorimotor network (including the supplementary motor cortex). ROC analysis identified the highest classification power in the thalamic network. CONCLUSIONS: Altered brain structures might be implicated in Mn overexposure-related disturbances in motivative modulation, cognitive control and information integration. These results encourage further studies that focus on the interaction mechanisms, including the basal ganglia network, thalamic network and default mode network. Our study identified potential neurobiological markers in Mn-exposed welders and illustrated the utility of a multivariate method of gray matter analysis.

Nanoemulsion based lipid nanoparticles for effective demethylcantharidin delivery to cure liver cancer.

Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit-8 (CCK-8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor-bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor-targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion-based lipid nanoparticle (NLNs)-efficient DEM delivery to treat liver cancer.