Streptococcus agalactiae isolated from clinical mastitis cases on large dairy farms in north China: phenotype, genotype of antimicrobial resistance and virulence genes.

Streptococcus agalactiae (Strep. agalactiae) is bovine mastitis pathogen and has thus became a matter of concern to dairy farms worldwide in terms of economic loss. The aims of this study were to (a) determine virulence genes, and (b) characterize the antimicrobial resistance (AMR) profiles and AMR genes and (c) figure out the relationship between AMR phenotypes and genotypes of Strep. agalactiae isolated from dairy cows in north China. A total of 20 virulence genes and 23 AMR genes of 140 isolates collected from 12 farms in six provinces were studied. The antimicrobial susceptibility of 10 veterinary commonly used antimicrobials were tested using the broth microdilution method. Results showed that all the isolates harbored the virulence genes lacIV, gapC, and dltA. The isolates that harbored the genes lacIII, fbsA, hylB, and cfb exhibited the high prevalence (99.29%), followed by isolates that harbored lacI (98.57%), bibA (97.86%), cylE (97.14%), lacII (92.14%), cspA (52.14%), pavA (25%), bca (2.14%), and scpB (0.71%). The fbsB, lmb, spbI, bac, and rib genes were not detected. The virulence patterns of B (fbsA_cfb_cylE_ hylB_bibA_cspA_ gapC_dltA_lacIII/IV) and C (fbsA_cfb_ bibA _ gapC_ dltA_lacIV) were dominant, accounting for 97.86% of the isolates. The following AMR genes were prevalent: pbp1A (97.14%), tet(M) (95.00%), lnu (A) (80.71%), erm (B) (75.00%), tet(O) (72.14%), blaZ (49.29%), tet(S) (29.29%), blaTEM (25.71%), erm (A) (17.14%), erm (C) (13.57%), tet (L) (10.71%), linB (2.86%), and erm (TR) (2.86%). The pbp2b, mecA1, mecC, lnu (D), erm (F/G/Q), and mef (A) genes were not detected. Eighty percent of the isolates harbored AMR genes and were highly resistant to tetracycline, followed by macrolides (10.71%), lincosamides (9.29%) and ß-lactams (4.29%). In conclusion, isolates only exhibited well correlation between tetracyclines resistance phenotype and genotype, and almost all isolates harbored intact combination of virulence genes.

Ni@TiO2 nanoribbon array electrode for high-efficiency non-enzymatic glucose biosensing.

The exploration of noble metal-free nanoarrays as high-activity catalytic electrodes for glucose biosensing holds great significance. Herein, we propose a Ni nanoparticle-decorated TiO2 nanoribbon array on a titanium plate (Ni@TiO2/TP) as an effective non-enzymatic glucose biosensing electrode. The as-prepared Ni@TiO2/TP electrode demonstrates rapid glucose response, a wide linear response range (1 µM to 1 mM), a low detection limit (0.08 µM, S/N = 3), and high sensitivity (10 060 and 3940 µA mM-1 cm-2), with good mechanical flexibility and stability. Moreover, it proves efficient in glucose biosensing in real human blood serum and cell culture fluid. Thus, it is highly promising for practical applications.

Differences in preimplantation blastocyst chromosomal aberrations between polycystic ovary syndrome women and controls: a multi-center retrospective cohort study.

PURPOSE: Comprehensive chromosomal status of blastocyst from women with polycystic ovary syndrome (PCOS) was limited. This study aimed to identify possible differences in the preimplantation blastocyst chromosome aberrations between PCOS women and controls receiving preimplantation genetic testing (PGT). METHODS: This was a multi-center retrospective cohort study including a total of 707 blastocysts from 147 PCOS women and 3006 blastocysts from 821 control women receiving PGT between 2015 and 2021. Embryonic chromosomal aberration spectrums were compared between PCOS and controls. Mixed effects generalized linear model was conducted to explore possible influence of PCOS-related endocrinological disorders on embryonic chromosomal abnormalities. RESULTS: Blastocysts from PCOS demonstrated significantly lower aneuploidy rate (15.2% vs. 25.2% per women, P < 0.001; 14.7% vs. 25.4% per blastocyst, P < 0.001) but greater mosaicism rate (12.5% vs. 8.0% per women, P = 0.007; 16.5% vs. 8.7% per blastocyst, P < 0.001). Mixed effects generalized linear model identified PCOS as an independent protective factor against embryonic aneuploidy (adjusted odds ratio = 0.68, 95% confidence interval, 0.50-0.93, P = 0.014) but a risk factor for embryonic mosaicism (adjusted odds ratio = 1.52, 95% confidence interval 1.11-2.10, P = 0.009). Further model analysis suggested that insulin resistance could be responsible for the increased risk of embryonic mosaicism among PCOS women (adjusted odds ratio = 2.17, 95% confidence interval, 1.10-4.31, P = 0.026). CONCLUSION: PCOS is associated with a lower aneuploidy risk but an increased mosaicism risk in preimplantation blastocysts, and insulin resistance should be investigated as a potential cause.

Diversity of soybean rhizobia in Northeast China and their application.

Biological nitrogen fixation is the main source of nitrogen in ecosystems. The diversity of soil rhizobia and their effects on soybeans need further research. In this study, we collected soybean rhizosphere samples from eight sites in the black soil soybean planting area in Northeast China. A total of 94 strains of bacteria were isolated and identified using the 16S rRNA and symbiotic genes (nodC, nifH) analysis, of which 70 strains were identified as rhizobia belonging to the genus Bradyrhizobium. To further validate the application effects of rhizobia, we selec-ted seven representative indigenous rhizobia based on the results of phylogenetic analysis, and conducted laboratory experiments to determine their nodulation and the impacts on soybeans. The results showed that, compared to the control without rhizobial inoculation, all the seven indigenous rhizobia exhibited good promoting and nodulation abilities. Among them, strains H7-L22 and H34-L6 performed the best, with the former significantly increasing plant height by 25.7% and the latter increasing root nodule dry weight by 20.9% to 67.1% compared to other indi-genous rhizobia treatments. We tested these two efficient rhizobia strains as soybean rhizobial inoculants in field experiments. The promoting effect of mixed rhizobial inoculants was significantly better than single ones. Compared to the control without inoculation, soybean yield increased by 8.4% with the strain H7-L22 treatment and by 17.9% with the mixed inoculant treatment. Additionally, there was a significant increase in the number of four-seed pods in soybeans. In conclusion, the application of rhizobial inoculants can significantly increase soybean yield, thereby reducing dependence on nitrogen fertilizer during soybean production, improving soil health, and promoting green development in agriculture in the black soil region of Northeast China.

Unveiling Cuproptosis: Mechanistic insights, roles, and leading advances in oncology.

Copper, a vital micronutrient, performs essential functions in numerous biological settings. Its disrupted metabolism is implicated in both the initiation of tumors and therapeutic interventions for cancer, underscoring the critical necessity of preserving copper homeostasis. Cuproptosis, a regulated cell death (RCD) modulated by copper, is activated in response to elevated copper concentrations, prompting an investigation into its implication in oncogenesis. Within this review, an exploration is conducted into copper dynamics and homeostasis maintenance within cells. Furthermore, it delves into the mechanisms underlying cuproptosis and its interplay with signaling pathways implicated in cancer. The potential synergy between cuproptosis and ferroptosis and its impact on tumor immunomodulation is discussed. Additionally, promising avenues for addressing cuproptosis in cancer involve assessing the utility of copper chelators and ionophores. By addressing pressing questions surrounding cuproptosis and outlining its pivotal role in cancer pathogenesis and treatment, this review propounds targeting cuproptosis as a promising frontier in antitumor therapy, potentially revolutionizing cancer treatment strategies.

Immuno-Rolling Circle Amplification (Immuno-RCA): Biosensing Strategies, Practical Applications, and Future Perspectives.

In the rapidly evolving field of life sciences and biomedicine, detecting low-abundance biomolecules, and ultraweak biosignals presents significant challenges. This has spurred a rapid development of analytical techniques aiming for increased sensitivity and specificity. These advancements, including signal amplification strategies and the integration of biorecognition events, mark a transformative era in bioanalytical precision and accuracy. A prominent method among these innovations is immuno-rolling circle amplification (immuno-RCA) technology, which effectively combines immunoassays with signal amplification via RCA. This process starts when a targeted biomolecule, such as a protein or cell, binds to an immobilized antibody or probe on a substrate. The introduction of a circular DNA template triggers RCA, leading to exponential amplification and significantly enhanced signal intensity, thus the target molecule is detectable and quantifiable even at the single-molecule level. This review provides an overview of the biosensing strategy and extensive practical applications of immuno-RCA in detecting biomarkers. Furthermore, it scrutinizes the limitations inherent to these sensors and sets forth expectations for their future trajectory. This review serves as a valuable reference for advancing immuno-RCA in various domains, such as diagnostics, biomarker discovery, and molecular imaging.

AD16 attenuates neuroinflammation induced by cerebral ischemia through down-regulating astrocytes A1 polarization.

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial. In this study, we utilized a rat model of transient middle cerebral artery occlusion (tMCAO) to explore whether the anti-inflammatory compound AD16 protects against ischemic brain injury by regulating A1 polarization and its underlying mechanisms. Our results showed that AD16 treatment significantly reduced the brain infarcted volume and improved neurological function in tMCAO rats. GO analysis results show that differential genes among the Sham, tMCAO and AD16 treatment groups are involved in the regulation of cytokine and inflammatory response. KEGG enrichment pathways analysis mainly enriched in cytokine-cytokine receptor interaction, viral protein interaction with cytokine-cytokine receptor, TNF, chemokine, NF-κB and IL-17 signaling pathway. Furthermore, AD16 treatment decreased the permeability of the blood-brain barrier and suppressed neuroinflammation. AD16 treatment also significantly reduced the polarization of A1 and inhibited NF-κB and JAK2/STAT3 signaling pathways. This study demonstrates that AD16 protects against brain injury in ischemic stroke by reducing A1 polarization to suppress neuroinflammation through downregulating NF-κB and JAK2/STAT3 signaling. Our findings uncover a potential molecular mechanism for AD16 and suggest that AD16 holds promising therapeutic potential against cerebral ischemia.

Diagnostic and screening potential of plasma exosome miR­99b­5p and its combination with other miRNAs for colorectal cancer.

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

Changing ozone sensitivity in Fujian Province, China, during 2012-2021: Importance of controlling VOC emissions.

In the troposphere, ozone (O3) formation can be limited by NOx, VOCs, or both, complicating efforts to reduce O3 by controlling its precursors. This study used formaldehyde (HCHO) data and nitrogen dioxide (NO2) data from the Ozone Monitoring Instrument (OMI) to analyze O3 formation sensitivity in Fujian from 2012 to 2021. Over the past decade, an 8.7% reduction in NO2 VCDs and a 9.91% increase in HCHO VCDs were observed. Due to differences in the primary driving factors, HCHO VCDs exhibit a characteristic seasonal pattern with higher in summer and lower in winter, whereas NO2 VCDs show the opposite trend. O3 formation chemistry was accurately diagnosed by combining satellite-based data and ground-based O3 data. A new threshold value (3.3-4.6) was derived to determine the transition from VOC-limited to NOx-limited O3 formation regimes. Results showed that O3 sensitivity exhibited pronounced seasonal variations. The VOC-limited regime predominates throughout the entire Fujian region in winter, whereas it occupies only 5% of the area in summer. A VOC-limited region was found widely across Fujian on an annual average, but it decreased by 24% over 10 years. Transitional areas experienced a 19% increase. In two natural emission reduction cases (reductions during the Chinese Lunar New Year holiday and reductions in weekend traffic emissions compared to weekdays), ground-level O3 effectively captured the impacts of sensitivity changes. The impact suggests that when Fujian is in the VOC control region, a significant reduction in NOx, without effective VOC control, might lead to an O3 increase. The importance of controlling VOC emissions is highlighted in Fujian. This study enhances the understanding of O3 formation regimes in southeastern China, which is crucial for developing O3 prevention and control strategies.

Learning functional brain networks with heterogeneous connectivities for brain disease identification.

Functional brain networks (FBNs), which are used to portray interactions between different brain regions, have been widely used to identify potential biomarkers of neurological and mental disorders. The FBNs estimated using current methods tend to be homogeneous, indicating that different brain regions exhibit the same type of correlation. This homogeneity limits our ability to accurately encode complex interactions within the brain. Therefore, to the best of our knowledge, in the present study, for the first time, we propose the existence of heterogeneous FBNs and introduce a novel FBN estimation model that adaptively assigns heterogeneous connections to different pairs of brain regions, thereby effectively encoding the complex interaction patterns in the brain. Specifically, we first construct multiple types of candidate correlations from different views or based on different methods and then develop an improved orthogonal matching pursuit algorithm to select at most one correlation for each brain region pair under the guidance of label information. These adaptively estimated heterogeneous FBNs were then used to distinguish subjects with neurological/mental disorders from healthy controls and identify potential biomarkers related to these disorders. Experimental results on real datasets show that the proposed scheme improves classification performance by 7.07% and 7.58% at the two sites, respectively, compared with the baseline approaches. This emphasizes the plausibility of the heterogeneity hypothesis and effectiveness of the heterogeneous connection assignment algorithm.

A comprehensive chemotyping and gonadal regulation of seven kisspeptinergic neuronal populations in the mouse brain.

Herein, we present a systematic analysis, using dual and multiplex RNAscope methods, of seven kisspeptinergic neuronal populations, based on their chemotyping and distribution throughout the mouse brain. The co-expression of mRNAs coding for neuropeptides, for excitatory and inhibitory transmitter vesicular transporters, and for sex steroid receptors are described in four hypothalamic and three extra-hypothalamic nuclei. These include a newly characterized kisspeptin-expressing ventral premammillary nucleus cell group co-expressing vesicular glutamate transporter 2, pituitary adenylate cyclase-activating polypeptide and neurotensin mRNAs. Kisspeptin mRNA ( Kiss1) was observed within both somatic and dendritic compartments at a single-cell level in two hypothalamic sites, a prominent and previously undescribed feature of kisspeptin neurons in these two cell groups. Patterns of altered Kiss1 expression following gonadectomy among these seven KP populations suggest that androgen receptor signaling may also play a previously unremarked role in gonadal feedback regulation of kisspeptinergic neuronal function. Data from this study provide a chemoanatomical basis for hypothesis generation regarding the functional diversity of kisspeptinergic signaling in hypothalamic and extrahypothalamic brain.

Whole genome sequencing insight into carbapenem-resistant and multidrug-resistant Acinetobacter baumannii harboring chromosome-borne blaOXA-23.

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure "ISAba1-blaADC-25." The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.

Morphological Signatures of Neurogenesis and Neuronal Migration in Hypothalamic Vasopressinergic Magnocellular Nuclei of the Adult Rat.

The arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker (Ionized calcium binding adaptor molecule 1, Iba1), and 5'-bromo-2'-deoxyuridine (BrdU), we report morphological evidence that low-rate neurogenesis and migration occur in adult AVPMNS in the rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the supraaoptic (SON) and paraventricular (PVN) nuclei. These findings raise new questions about AVPMNS's potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.

Silica nanoparticle design for colorectal cancer treatment: Recent progress and clinical potential.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.

Graph Convolutional Network with Self-supervised Learning for Brain Disease Classification.

Brain functional network (BFN) analysis has become a popular method for identifying neurological diseases at their early stages and revealing sensitive biomarkers related to these diseases. Due to the fact that BFN is a graph with complex structure, graph convolutional networks (GCNs) can be naturally used in the identification of BFN, and can generally achieve an encouraging performance if given large amounts of training data. In practice, however, it is very difficult to obtain sufficient brain functional data, especially from subjects with brain disorders. As a result, GCNs usually fail to learn a reliable feature representation from limited BFNs, leading to overfitting issues. In this paper, we propose an improved GCN method to classify brain diseases by introducing a self-supervised learning (SSL) module for assisting the graph feature representation. We conduct experiments to classify subjects with mild cognitive impairment (MCI) and autism spectrum disorder (ASD) respectively from normal controls (NCs). Experimental results on two benchmark databases demonstrate that our proposed scheme tends to obtain higher classification accuracy than the baseline methods.

Genetic and molecular characterization of H9N2 avian influenza viruses in Yunnan Province, Southwestern China.

The H9N2 subtype of the avian influenza virus (AIV) is widely prevalent in birds, threatening the poultry industry and providing genetic material for emerging human pathogens. The prevalence and genetic characteristics of H9N2 in Yunnan Province, China, are largely unknown. Samples were collected from live poultry markets (LPMs) and breeding farms in Yunnan Province. H9N2-positive samples were identified by polymerase chain reaction (PCR), with a high positivity rate of 42.86% in tissue samples. The positivity rate of swab samples in the LPMs in Kunming was 3.97% (17/564), but no AIV was detected in samples from poultry farms in Lijiang, Wenshan, and Yuxi. Evolutionary analysis and genotyping were performed for the 17 strains of isolated H9N2 virus. Phylogenetic analysis revealed that all H9N2 viral genes had 91.6%-100% nucleotide homology, belonged to the G57 genotype, and had high homology with H9N2 viruses isolated from Guangdong and Guangxi, suggesting that the H9N2 viruses in Yunnan Province may have been imported by chicks. Using a nucleotide divergence cutoff of 95%, we identified ten distinct H9N2 genotypes that continued to evolve. The surface genes of the H9N2 isolates displayed substantial genetic diversity, highlighting the genetic diversity and complexity of the H9N2-subtype AIVs in Yunnan. Molecular analysis demonstrated that all 17 strains of H9N2 isolates had mutations at H183N, Q226L, L31P, and I268V in hemagglutinin; S31N in matrix protein 2; and no replacements at positions 274 and 292 of the neuraminidase protein. Sixteen strains had the A558V mutation and one strain had the E627V mutation in polymerase basic protein 2. Analysis of these amino acid sites suggests that H9N2 influenza viruses in Yunnan continue to mutate and adapt to mammals and are sensitive to neuraminidase inhibitors but resistant to adamantanes. It is necessary to strengthen surveillance of AIV H9N2 subtypes in poultry and LPMs in Yunnan to further understand their genetic diversity.

Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

Analysis of spiritual well-being status and influencing factors in patients with esophageal cancer: a cross-sectional study.

OBJECTIVE: To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS: A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS: The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS: The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.

Ion-sensitive field effect transistor biosensors for biomarker detection: current progress and challenges.

The ion-sensitive field effect transistor (ISFET) has emerged as a crucial sensor device, owing to its numerous benefits such as label-free operation, miniaturization, high sensitivity, and rapid response time. Currently, ISFET technology excels in detecting ions, nucleic acids, proteins, and cellular components, with widespread applications in early disease screening, condition monitoring, and drug analysis. Recent advancements in sensing techniques, coupled with breakthroughs in nanomaterials and microelectronics, have significantly improved sensor performance. These developments are steering ISFETs toward a promising future characterized by enhanced sensitivity, seamless integration, and multifaceted detection capabilities. This review explores the structure and operational principles of ISFETs, highlighting recent research in ISFET biosensors for biomarker detection. It also examines the limitations of these sensors, proposes potential solutions, and anticipates their future trajectory. This review aims to provide a valuable reference for advancing ISFETs in the field of biomarker measurement.

Salidroside Inhibits α-Amanitin-Induced AML-12 Cell Apoptosis via the Regulation of PINK1/Parkin-Mediated Mitophagy and Mitochondrial Function.

Poisoning caused by the mushroom Amanita phalloides, due to the toxin α-amanitin, accounts for approximately 90% of food poisoning deaths in China with no specific antidotes. To investigate the role of salidroside (Sal) in α-amanitin (α-AMA)-induced mitophagy, mouse liver cells AML-12 were exposed to α-AMA in the presence of Sal or not. Intracellular reactive oxygen species (ROS) levels were measured using a ROS detection kit, mitochondrial activity was evaluated using a mitochondrial red fluorescent probe kit or JC-1 dye, and protein expression levels of PINK1, Parkin, LC3 II, P62, Bax, Bcl-2, Caspase 3, Cleaved-Caspase 3, PARP I, and Cleaved-PARP I were detected through Western blot. Results demonstrated that α-AMA led to increased intracellular ROS levels, cell apoptosis, and decreased mitochondrial membrane potential. Notably, expression levels of mitophagy-related proteins PINK1, Parkin, and LC3 increased significantly while the P62 protein expression decreased remarkably. Furthermore, Sal reversed the α-AMA-induced decrease in cell viability and mitochondrial membrane potential and increase in intracellular ROS level. In addition, Sal promoted expression levels of PINK1, Parkin, and LC3 II while suppressing the Bax/Bcl-2 ratio, Cleaved-Caspase 3, and Cleaved-PARP I as well as P62. The results above proved that salidroside alleviates α-AMA-induced mouse liver cells damage via promoting PINK1/Parkin-mediated mitophagy and reducing cell apoptosis.