Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.

Rapid species-level metagenome profiling and containment estimation with sylph.

Profiling metagenomes against databases allows for the detection and quantification of microorganisms, even at low abundances where assembly is not possible. We introduce sylph, a species-level metagenome profiler that estimates genome-to-metagenome containment average nucleotide identity (ANI) through zero-inflated Poisson k-mer statistics, enabling ANI-based taxa detection. On the Critical Assessment of Metagenome Interpretation II (CAMI2) Marine dataset, sylph was the most accurate profiling method of seven tested. For multisample profiling, sylph took >10-fold less central processing unit time compared to Kraken2 and used 30-fold less memory. Sylph's ANI estimates provided an orthogonal signal to abundance, allowing for an ANI-based metagenome-wide association study for Parkinson disease (PD) against 289,232 genomes while confirming known butyrate-PD associations at the strain level. Sylph took <1 min and 16 GB of random-access memory to profile metagenomes against 85,205 prokaryotic and 2,917,516 viral genomes, detecting 30-fold more viral sequences in the human gut compared to RefSeq. Sylph offers precise, efficient profiling with accurate containment ANI estimation even for low-coverage genomes.

Associations of arterial oxygen partial pressure with all­cause mortality in critically ill ischemic stroke patients: a retrospective cohort study from MIMIC IV 2.2.

BACKGROUND: As a supportive treatment, the effectiveness of oxygen therapy in ischemic stroke (IS) patients remains unclear. This study aimed to evaluate the relationships between arterial partial pressure of oxygen (PaO2) and both consciousness at discharge and all-cause mortality risk in ICU IS patients. METHODS: Blood gas measurements for all patients diagnosed with IS were extracted from the MIMIC-IV database. Patients were classified into four groups based on their average PaO2 during the first ICU day: hypoxemia (PaO2 < 80 mmHg), normoxemia (PaO2 80-120 mmHg), mild hyperoxemia (PaO2 121-199 mmHg), and moderate/severe hyperoxemia (PaO2 ≥ 200 mmHg). The primary endpoint was 90-day all-cause mortality. Secondary outcomes included the level of consciousness at discharge, assessed by the Glasgow Coma Scale (GCS), and 30-day all-cause mortality. Multivariate Cox regression and Restricted cubic spline (RCS) analysis were used to investigate the relationship between mean PaO2 and mortality, and to assess the nonlinear association between exposure and outcomes. RESULTS: This study included a total of 946 IS patients. The cumulative incidence of 30-day and 90-day all-cause mortality increased with decreasing PaO2 levels. RCS analysis revealed a nonlinear relationship between PaO2 and the risk of 30-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001), as well as a nonlinear association between PaO2 and 90-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001). The results remained consistent after excluding the small subset of patients who received reperfusion therapy. Sensitivity analysis indicated that the favorable impact on survival tends to increase with the extended duration of elevated PaO2. CONCLUSIONS: For IS patients who do not receive reperfusion therapy or whose recanalization status is unknown, a lower PaO2 early during ICU admission is considered an independent risk factor for short-term and recent mortality. Adjusting respiratory parameters to maintain supraphysiological levels of PaO2 appears to be beneficial for survival, although this finding requires further validation through additional studies. TRIAL REGISTRATION: Not applicable.

The Addition of Hot Water Extract of Juncao-Substrate Ganoderma lucidum Residue to Diets Enhances Growth Performance, Immune Function, and Intestinal Health in Broilers.

The purpose of this experiment was to investigate the effects of Hot Water Extract of Juncao-substrate Ganoderma lucidum Residue (HWE-JGLR) on the immune function and intestinal health of yellow-feather broilers. In an animal feeding experiment, 288 male yellow-feather broilers (1 day old) were randomly allocated to four treatment groups with six replicates of 12 birds each. The control (CON) group was fed a basal diet. HJ-1, HJ-2, and HJ-3 were fed a basal diet supplemented with 0.25%, 0.50%, and 1.00% HWE-JGLR, respectively. The feeding trial lasted for 63 d. The results showed increased ADFI (p = 0.033) and ADG (p = 0.045) of broilers in HJ-3, compared with the CON group. Moreover, higher contents of serum IL-4 and IL-10 and gene expression of IL-4 and IL-10 in jejunum mucosa and lower contents of serum IL-1ß and gene expression of IL-1ß in jejunum mucosa in HJ-3 were observed (p < 0.05). Additionally, the jejunal mucosal gene expression of Claudin-1 and ZO-1 in HJ-2 and HJ-3 was higher than that in the CON group (p < 0.05). As for the microbial community, compared with the CON group, the ACE index, Shannon index, and Shannoneven index of cecal microorganisms in HJ-2 and HJ-3 were elevated (p < 0.05). PCoA analysis showed that the cecal microbial structure of broilers in HJ-2 and HJ-3 was different from the CON group (p < 0.05). In contrast with the CON group, the broilers in HJ-2 and HJ-3 possessed more abundant Desulfobacterota at the phylum level and unclassified Lachnospiraceae, norank Clostridia vadinBB60 group and Blautia spp. at the genus level, while Turicibacter spp. and Romboutsia spp. were less (p < 0.05). In conclusion, dietary supplementation with HWE-JGLR can improve growth performance, enhance body immunity and intestinal development, and maintain the cecum microflora balance of yellow-feather broilers.

Formononetin Mitigates Liver Fibrosis via Promoting Hepatic Stellate Cell Senescence and Inhibiting EZH2/YAP Axis.

Formononetin (FMN), an isoflavone mainly derived from leguminous plants, is a natural secondary metabolite with valuable pharmacological effects in the regulation of numerous chronic diseases. This study aimed to investigate the influence of FMN on liver fibrosis and clarify the underlying mechanisms. In vivo FMN administration protected mice from BDL or CCl4-induced liver fibrosis. In vitro experimental findings revealed the FMN-mediated inhibitory effects on hepatic stellate cell (HSC) activation. Transcriptome analyses showed that YAP silencing and the subsequent HSC senescence might be responsible for the FMN-mediated antifibrotic outcomes. Furthermore, FMN suppressed EZH2 and its substrate H3K27me3, which are essential for YAP activation and HSC senescence. Remarkably, EZH2 overexpression reversed the FMN potential therapeutic effects on YAP that impact HSC senescence. Our study demonstrated that FMN potentially mitigated hepatic fibrosis by inhibiting EZH2/YAP axis and promoting HSC senescence. Together, these findings provide insights into the prospective therapeutic targets of FMN in liver fibrosis management.

Development of theoretical framework and digital competence assessment checklist (DCAC) for nursing students.

Background: The rapid development of digital technology impacts all aspects, including nursing education. Nursing programs are tasked with equipping graduates with both clinical skills and digital competence. However, inconsistencies in the conceptual understanding of digital competence in nursing literature, underscore the need to refine the concept. Design: This study involved two phases including a modified Delphi approach and psychometric testing. In Phase 1, the panel of experts in nursing was invited to evaluate the theoretical framework, domain, and item of assessment checklist. In Phase 2, the psychometric properties of the assessment checklist were tested using a quantitative survey. Setting: The study was conducted in Taiwan, Indonesia, and Vietnam. Participant: Participants included 12 nursing experts from Taiwan, Indonesia, and Vietnam during the development phase and 417 nursing students from these countries in the validation phase. Methods: Phase 1 utilized a modified Delphi approach establishing a theoretical framework and assessment checklist. Experts provided feedback on a Likert scale, aiming for consensus. Phase 2 involved a quantitative survey where graduate nursing students rated the DCAC. The analysis process following the recommendation of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Results: The theoretical framework defined digital competence across four domains. In the first Delphi round, all items were rated above the consensus threshold. After two rounds, the CVI ranged from .8 to 1.0, suggesting strong agreement among experts. The second phase revealed high discriminant validity among survey items, with Cronbach's alpha indicating high internal consistency. The refined 22-item DCAC showed improved fit indices, confirming the assessment checklist's structure. Conclusion: The developed 22-item DCAC is a valid and reliable tool for measuring digital competence among nursing students. Integration of digital competence into nursing education is essential for preparing students to excel in the healthcare environment.

Meet-in-metabonomics: Insights into associations between hair heavy metal and adverse child growth in e-waste recycling area.

Heavy metal pollution from informal e-waste recycling may adversely affect child growth. However, the potential toxic mechanisms from a population perspective remain unknown. Herein, 18 hair heavy metals, urinary metabolomics, and three child growth indices [i.e., weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), and BMI Z-score (BMIZ)] were measured in children from e-waste recycling (ER, N = 426) and control areas (CR, N = 247). We examined longitudinal changes in heavy metal exposure and child growth after e-waste control to further elucidate causal relationships. Results showed that children in regulated ER site were still exposed to higher levels of several heavy metals and experienced poorer growth compared to those in control areas. Elevated exposure to heavy metals like tin, antimony, lead, cadmium, and cobalt correlated with poor child growth, particularly affecting girls and younger children. Tin, rather than traditionally concerning heavy metals, exhibited the most crucial role in driving the adverse effects of metal mixtures on child growth. Reducing heavy metal exposure through e-waste control could notably improve child growth, confirming the causal relationship between heavy metal exposure and poor child growth and underscoring the health benefits of e-waste regulation. Our research identified the roles of steroid biosynthesis, folate biosynthesis, amino acid metabolism, and purine metabolism in mediating the effects of metal exposure on child growth. Testosterone glucuronide, riboflavin, folic acid, xanthosine, and xanthine emerged as key mediators, potentially serving as metabolic signatures of heavy metal exposure. These findings illuminate the toxic mechanisms underlying poor child growth resulted from heavy metal exposure, offering important insights from a population-based perspective. In addition to lead and cadmium, monitoring and regulating tin and antimony are crucial to mitigate their negative impact on child growth in e-waste recycling areas.

Study on the Flexural Deformation Behavior of High-Titanium Heavy-Slag Concrete Composite Beams: Material Application, Experimental Investigation, and Theoretical Refinement.

To investigate the flexural performance of high-titanium heavy-slag concrete composite beams under loading, this study examined the impact of various factors on deflection development and crack propagation as well as the applicability of empirical formulas for monolithic concrete beams. Seven concrete beams were fabricated with variables such as the reinforcement ratio, prefabrication height, and material composition, and were subjected to two-point concentrated loading. By comparing deflection values and crack widths during loading and analyzing the correlations with empirical formulas from standards, theoretical formulas with significant deviations were modified and compared. The study indicated that the cracking moment and deflection correlated with the reinforcement ratio, material structure combination, and composite height. The empirical formulas for the maximum crack width and deflection of flexural members were applicable to high-titanium heavy-slag concrete composite beams, although some discrepancies existed compared with the experimental values. After modifications, these discrepancies were reduced. This research provides a comprehensive analysis of the deformation characteristics and fracture behavior of high-titanium heavy-slag concrete composite beams.

A study on user willingness to participate in an adverse drug event information sharing system.

BACKGROUND: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea. METHODS: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis. RESULTS: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively. CONCLUSIONS: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment.

Beyond skin deep: Revealing the essence of iPS cell-generated skin organoids in regeneration.

Various methods have been used for in vivo and in vitro skin regeneration, including stem cell therapy, tissue engineering, 3D printing, and platelet-rich plasma (PRP) injection therapy. However, these approaches are rooted in the existing knowledge of skin structures, which overlook the normal physiological processes of skin development and fall short of replicating the skin's regenerative processes outside the body. This comprehensive review primarily focuses on skin organoids derived from human pluripotent stem cells, which have the capacity to regenerate human skin tissue by restoring the embryonic skin structure, thus offering a novel avenue for producing in vitro skin substitutes. Furthermore, they contribute to the repair of damaged skin lesions in patients with systemic sclerosis or severe burns. Particular emphasis will be placed on the origins, generations, and applications of skin organoids, especially in dermatology, and the challenges that must be addressed before clinical implementation.

Interpretative structural modeling method: An analysis of influencing factors analysis on the adverse experiences of cardiac surgery patients in the intensive care units.

Objective: To construct an interpretation structure model of adverse experiences of cardiac surgery patients in intensive care unit, so as to provide a reference for optimizing the experience of critical patients step by step. Methods: Literature review, semi-structured interviews, questionnaires and Delphi method were used to summarize and analyze the influencing factors of intensive care experience in cardiac surgery. The explanatory structural model was used to divide the influencing factors into levels and construct the explanatory structural model of adverse experience of cardiac surgery patients in intensive care. Results: A hierarchical structure model containing 34 elements and 15 levels was constructed, which were divided into Surface level, middle level and root level. Conclusion: The intensive care experience of patients in cardiac surgery department is mainly affected by 34 factors. There are direct or indirect correlations between the influencing factors, and different levels have different effects.

Alleviating the volume expansion of silicon anodes by constructing a high-strength ordered multidimensional encapsulation structure.

The application of silicon-based nanomaterials in fast-charging scenarios is hindered by volume expansion during lithiation and side reactions induced by surface effects. Constructing a robust encapsulation structure with high mechanical strength and conductivity is pivotal for optimizing the electrochemical performance of nanostructured silicon anodes. Herein, we propose a multifaceted hierarchical encapsulation structure featuring excellent mechanical strength and high conductivity by sequentially incorporating SiO x , hard carbon, and closed-pore carbon layers around silicon quantum dots, thereby enabling stable cycling at high current densities. In this structure, the ultra-thin SiO x layer strengthens the Si-C interface, while the outermost carbon matrix with closed pores functions both as a conductive network and a barrier against electrolyte intrusion. Notably, the synthesized material exhibits a specific capacity of 1506 mA h g-1 with 90.17% retention after 300 cycles at 1.0 A g-1. After 500 cycles at 5.0 A g-1, it retains 640.4 mA h g-1, over 70% of its initial capacity.

Lipopolysaccharide Triggers Luminal Acidification to Promote Defense Against Bacterial Infection in Vaginal Epithelium.

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

Ganoderma lucidum polysaccharide promotes broiler health by regulating lipid metabolism, antioxidants, and intestinal microflora.

Ganoderma lucidum polysaccharides (GLP) are the primary bioactive macromolecular compounds of Ganoderma lucidum, possessing antioxidant and immunomodulatory effects. Hot water extract of Juncao-substrate Ganoderma Lucidum residue (HWE-JGLR) is abundant in GLP. There are few research reports on the application of HWE-JGLR in animal husbandry. Therefore, this study aims to investigate the effects of HWE-JGLR supplementation on growth performance, serum biochemistry, the antioxidant function of serum and liver, and the intestinal microbiota of yellow-feathered broilers. The control group was fed a corn-soybean meal basal diet, while the HJ I, II, and III groups received diets supplemented with 0.25 %, 0.5 %, and 1 % of HWE-JGLR, respectively. Results showed that HWE-JGLR increased the serum HDL-C content and decreased the TG content in broilers. Moreover, HWE-JGLR enhanced the antioxidant function by the Keap1-Nrf2/ARE signaling pathway and the antioxidative enzyme in broilers. In addition, the cecum of the metagenomic analysis of 16S rRNA showed that the relative abundance of no-rank Ruminococcacea was increased in the HJ I group. Our findings indicate that HWE-JGLR has strong potential for development as a green feed additive based on its functions of lipid-lowering, antioxidation, and the modulation of gut microbiota composition.

Revealing the links between hair metal(loids) and alterations in blood pressure among children in e-waste recycling areas through urinary metabolomics.

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure.

Dose Justification for Asciminib in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia with and Without the T315I Mutation.

BACKGROUND AND OBJECTIVE: Asciminib is approved in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) treated with ≥ 2 prior tyrosine kinase inhibitors. Here, we aimed to demonstrate similarity in efficacy/safety of asciminib 80 mg once daily (q.d.) versus 40 mg twice daily (b.i.d.) in patients with CML-CP without T315I mutation and support the use of the 200-mg b.i.d. dosage in patients harboring T315I, using model-informed drug development. METHODS: Data were collected from 199 patients in the phase I (NCT02081378; 10-200 mg b.i.d. or 10-400 mg q.d.) and 154 patients in the phase III (NCT03106779; 40 mg b.i.d.) studies. Evaluations were based on population pharmacokinetics (PopPK) and exposure-response (efficacy/safety) analyses. RESULTS: PopPK showed comparable exposure (area under the curve, AUC0-24h) for 40 mg b.i.d. and 80 mg q.d. (12,638 vs 12,646 ng*h/mL); average maximum and minimum plasma concentrations for 80 mg q.d. were 1.61- and 0.72-fold those of 40 mg b.i.d., respectively. Exposure-response analyses predicted similar major molecular response rates for 40 mg b.i.d. and 80 mg q.d. (Week 24: 27.6% vs 24.8%; Week 48: 32.3% vs 30.6%). Results also established adequacy of 200 mg b.i.d. in patients with T315I mutation (Week 24: 20.7%; Week 48: 23.7%), along with a similar safety profile for all dose regimens. CONCLUSIONS: Similarity between 40 mg b.i.d. and 80 mg q.d. regimens was investigated, demonstrating similar and substantial efficacy with well-tolerated safety in patients without T315I mutation. The 200-mg b.i.d. dose was deemed safe and effective for patients with T315I mutation.

A systematic review and meta-analysis on the transcriptomic signatures in alcohol use disorder.

Currently available clinical treatments on alcohol use disorder (AUD) exhibit limited efficacy and new druggable targets are required. One promising approach to discover new molecular treatment targets involves the transcriptomic profiling of brain regions within the addiction neurocircuitry, utilizing animal models and postmortem brain tissue from deceased patients with AUD. Unfortunately, such studies suffer from large heterogeneity and small sample sizes. To address these limitations, we conducted a cross-species meta-analysis on transcriptome-wide data obtained from brain tissue of patients with AUD and animal models. We integrated 36 cross-species transcriptome-wide RNA-expression datasets with an alcohol-dependent phenotype vs. controls, following the PRISMA guidelines. In total, we meta-analyzed 964 samples - 502 samples from the prefrontal cortex (PFC), 282 nucleus accumbens (NAc) samples, and 180 from amygdala (AMY). The PFC had the highest number of differentially expressed genes (DEGs) across rodents, monkeys, and humans. Commonly dysregulated DEGs suggest conserved cross-species mechanisms for chronic alcohol consumption/AUD comprising MAPKs as well as STAT, IRF7, and TNF. Furthermore, we identified numerous unique gene sets that might contribute individually to these conserved mechanisms and also suggest novel molecular aspects of AUD. Validation of the transcriptomic alterations on the protein level revealed interesting targets for further investigation. Finally, we identified a combination of DEGs that are commonly regulated across different brain tissues as potential biomarkers for AUD. In summary, we provide a compendium of genes that are assessable via a shiny app, and describe signaling pathways, and physiological and cellular processes that are altered in AUD that require future studies for functional validation.

Label-free detection of the cytotoxicity effect of cisplatin in human leukemic cells using Raman spectroscopy in conjunction with multivariate analysis.

The single-cell Raman spectra of human leukemic Jurkat cells can be obtained by confocal microscopy Raman spectroscopy, including cell groups treated with different doses of cisplatin (0, 3.5, 7, 10.5 and 14 µmol L-1) for 24 hours and those treated with 10.5 µmol L-1 cisplatin for different times (0, 6, 12, 24 and 36 hours). The structure and amount of protein, nucleic acid and other major molecules from different cell groups show special changes in the percentage of biochemical constituents. Compared with the control group, the two protein Raman bands (1449 and 1659 cm-1) and two DNA bands (1303 and 1338 cm-1) in the treatment groups decrease in intensity with the increase of the drug dose and treatment time of cisplatin. Partial least squares combined with support vector machines was used to develop diagnostic algorithms for distinguishing between control and treatment groups. The support vector machines for classification between the control group (0 µmol L-1) and cell groups treated with 10.5 and 14 µmol L-1 cisplatin for 24 hours have achieved good diagnostic results with a high sensitivity of 100%, specificity of 100% and accuracy of 100%, respectively, indicating that 10.5 µmol L-1 can be used as an appropriate therapeutic dose. Using the same method, the diagnostic sensitivity, specificity and accuracy between the control group (0 hours) and cell groups treated with 10.5 µmol L-1 cisplatin for 24 and 36 hours are all 100%, showing that 24 hours can be used as an appropriate therapeutic time. These results showed that Raman spectroscopy in conjunction with multivariate statistical analysis could be a useful tool for evaluating the cytotoxicity induced by cisplatin in human leukemic cells.

The Complete Mitochondrial Genome and Phylogenetic Analysis of Rhagastis binoculata (Matsumura, 1909) (Lepidoptera: Sphingidae).

The mitochondrial genome (mitogenome) Rhagastis binoculata (Matsumura, 1909), an endemic moth species in Taiwan, was sequenced and analyzed. The complete circular mitogenome of R. binoculata is 15,303 bp and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region. The mitogenome has an overall nucleotide composition of 41.2% A, 11.9% C, 7.5% G, and 39.4% T, with an AT content of 80.6%. Of the protein-coding genes (PCGs), 12 start with ATG, ATT, and ATC, and COX1 starts with a "CGA" codon. All of the stop codons are "TAA, TAG, or T". Our phylogenetic analysis of 21 species of Sphingidae insects suggests that R. binoculata is clustered with Rhagastis mongoliana, which belongs to the subfamily Macroglossinae.

Pulsed sounds caused by internal oxygen transport during photosynthesis in the seagrass Halophila ovalis.

Oxygen bubbles that leak from seagrass blades during photosynthesis have been hypothesized to cause cavitation sounds in aquatic plants. Here we investigate low-amplitude sounds with regular pulse rates produced during photosynthesis in seagrass beds of Halophila ovalis (Qitou Bay, Penghu islands and Cigu Lagoon, Taiwan). Sound pulses appear in the morning when illumination exceeds 10,000 Lux, peak at midday and decrease in midafternoon on a sunny day. Frequencies peak between 1 to 4 kHz, durations range between ca. 1.8 to 4.8 ms, and sound pressure level 1 cm from the bed is 105.4 ± 0.5 dB re 1 µPa (1100 h on a cloudy day). Sounds attenuate rapidly with distance, disappearing beyond 15 cm. Blocking sunlight or administering herbicide stops ongoing sounds. Gas bubbles are not typically seen during sound production ruling out cavitation, and external force (scissor cutting or plant pressed against the substrate) applied to the patch, leaves, petioles, or rhizomes generally increases pulse rate. We suggest sound emission is caused by internal oxygen transport through pores in diaphragms (a whistle mechanism) at the leaf base and nodes of the rhizome.