Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis.

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice.

Rat primary cortical cell tri-culture to study effects of amyloid-beta on microglia function.

Introduction: The etiology and progression of sporadic Alzheimer's Disease (AD) have been studied for decades. One proposed mechanism is that amyloid-beta (Aß) proteins induce neuroinflammation, synapse loss, and neuronal cell death. Microglia play an especially important role in Aß clearance, and alterations in microglial function due to aging or disease may result in Aß accumulation and deleterious effects on neuronal function. However, studying these complex factors in vivo , where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of microglia, astrocytes and neurons in the same culture. Here, we employ a tri-culture model of rat primary neurons, astrocytes, and microglia and compare it to co-culture (neurons and astrocytes) and mono-culture enriched for microglia to study microglial function (i.e., motility and Aß clearance) and proteomic response to exogenous Aß. Methods: We established cortical co-culture (neurons and astrocytes), tri-culture (neurons, astrocytes, and microglia), and mono-culture (microglia) from perinatal rat pups. On days in vitro (DIV) 7 - 14, the cultures were exposed to fluorescently-labeled Aß (FITC-Aß) particles for varying durations. Images were analyzed to determine the number of FITC-Aß particles after specific lengths of exposure. A group of cells were stained for ßIII-tubulin, GFAP, and Iba1 for morphological analysis via quantitative fluorescence microscopy. Cytokine profiles from conditioned media were obtained. Live-cell imaging with images acquired every 5 minutes for 4 hours was employed to extract microglia motility parameters (e.g., Euclidean distance, migration speed, directionality ratio). Results and discussion: FITC-Aß particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aß particles, as confirmed via epifluorescence and confocal microscopy. Adding FITC-Aß significantly increased the size of microglia, but had no significant effect on neuronal surface coverage or astrocyte size. Analysis of the cytokine profile upon FITC-Aß addition revealed a significant increase in proinflammatory cytokines (TNF-α, IL-1α, IL-1ß, IL-6) in tri-culture, but not co-culture. In addition, Aß addition altered microglia motility marked by swarming-like motion with decreased Euclidean distance yet unaltered speed. These results highlight the importance of cell-cell communication in microglia function (e.g., motility and Aß clearance) and the utility of the tri-culture model to further investigate microglia dysfunction in AD.

Recent developments in the use of nanocrystals to improve bioavailability of APIs.

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water-soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Loganin exerts neuroprotective effect by inhibiting neuronal pyroptosis in rat with cerebral haemorrhage.

Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague-Dawley rats were used, subjected to a collagenase-induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test. Results indicated a significant improvement in neurological functions in loganin-treated groups, evident from the mNSS and rotarod tests, suggesting dose-dependent neuroprotection. Loganin also effectively reduced the blood-brain barrier (BBB) permeability and cerebral oedema. Additionally, it mitigated cellular pyroptosis, as shown by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and western blot analysis, which indicated reduced levels of pyroptosis markers in treated rats. Furthermore, loganin's regulatory effects on the adenosine A2A receptor and myosin light chain kinase pathways were observed, potentially underpinning its protective mechanism against ICH. The study concludes that loganin exhibits significant neuroprotective properties in a rat ICH model, highlighting its potential as a novel therapeutic strategy. Despite promising results, the study needs further research to determine loganin's therapeutic potential in human ICH patients. This research paves the way for further exploration into loganin's clinical applications, potentially revolutionizing treatment strategies for patients suffering from intracerebral haemorrhage.

Sleep duration time and human papillomavirus infection risk: The U-shaped relationship revealed by NHANES data.

PURPOSE: This study aims to investigate the relationship between sleep factors (sleep duration time [SDT] and obstructive sleep apnea [OSA]) and human papillomavirus (HPV)/high-risk HPV(HR-HPV) infection, utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We conducted a cross-sectional analysis using NHANES data, focusing on SDT and OSA's association with HPV/HR-HPV infection. The primary statistical methods included weighted multivariate linear regression and logistic regression to assess the association between SDT, OSA, and HPV/HR-HPV infection. The study employed restricted cubic splines (RCS) for evaluating potential non-linear relationships between SDT and HPV/HR-HPV infection. Subgroup analyses were conducted. Interaction terms were used to examine the heterogeneity in associations across different subgroups. RESULTS: The study identified a U-shaped relationship between SDT and HPV infection. Specifically, 7 hours of sleep was associated with the lowest risk of HPV infection. In comparison, SDT less than 7 hours resulted in a 26.3% higher risk of HPV infection (Odds Ratio [OR] = 1.26, 95% Confidence Interval [CI]: 1.029, 1.549), and more than 9 hours of sleep showed a 57.4% increased risk (OR = 1.574, 95% CI: 1.116, 2.220). The relationship between SDT and HR-HPV infection was significant in the first two models, but not in the fully adjusted model. No significant interaction was found between sleep duration and other covariates. There was no association between OSA and HPV/HR-HPV infection. CONCLUSION: The study underscores the complex relationship between sleep duration and HPV infection risk, suggesting both very short and very long sleep durations may increase HPV infection likelihood. The findings highlight the need for further research to explore the biological mechanisms underpinning this association and to consider broader population groups and more precise sleep assessment methods in future studies.

Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption.

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT-qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHß and LHß in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Temperature-dependent excitonic emission characteristics of highly crystallized carbon nitride nanosheets.

Highly-crystallized carbon nitride (HCCN) nanosheets exhibit significant potential for advancements in the field of photoelectric conversion. However, to fully exploit their potential, a thorough understanding of fundamental excitonic photophysical processes is crucial. Here, the temperature-dependent excitonic photoluminescence (PL) of HCCN nanosheets and amorphous polymeric carbon nitride (PCN) is investigated using steady-state and time-resolved PL spectroscopy. The exciton binding energy of HCCN is determined to be 109.26 meV, lower than that of PCN (207.39 meV), which is attributed to the ordered stacking structure of HCCN with a weaker Coulomb interaction between electrons and holes. As the temperature increases, a noticeable reduction in PL lifetime is observed on both the HCCN and PCN, which is ascribed to the thermal activation of carrier trapping by the enhanced electron-phonon coupling effect. The thermal activation energy of HCCN is determined to be 102.9 meV, close to the value of PCN, due to their same band structures. Through wavelength-dependent PL dynamics analysis, we have identified the PL emission of HCCN as deriving from the transitions: σ*-LP, π*-π, and π*-LP, where the π*-LP transition dominants the emission because of the high excited state density of the LP state. These results demonstrate the impact of high-crystallinity on the excitonic emission of HCCN materials, thereby expanding their potential applications in the field of photoelectric conversion. .

Injury Mortality of Children and Adolescents Aged 0-19 Years - China, 2010-2021.

Introduction: To examine the recent trends in child injury mortality in China. Methods: Injury mortality data of 2010-2021 for children and adolescents aged 0-19 years were from the China Health Statistics Yearbook. Injury mortality disparities across urban vs. rural locations, gender, and age groups were scrutinized. Annual percent change (APC), average annual percent change (AAPC), and their 95% confidence intervals (95% CI) were estiamted usimg Joinpoint regression models. Results: The age-standardized injury mortality significantly dropped from 21.87 to 9.41 per 100,000 population among children and youth aged 0-19 years during 2010-2021, with an AAPC of -6.7% (95% CI: -8.2%, -5.2%). The urban-rural disparity and gender gap in injury mortality reduced gradually. In 2021, drowning and road traffic crashes were the top two causes of child injury deaths, explaing 31.1% and 27.9% of total injury deaths, respectively. Suffocation accounted for 62.3% of injury deaths among infants younger than a year. Alarmingly, the suicide mortality rate rose from 2.16 to 3.42 per 100,000 population between 2010 and 2021 among teenagers aged 15-19 years. Subgroup analyses yielded similar results. Conclusions: During 2010-2021, the injury mortality decreased significantly among Chinese children and adolescents, and the responding urban-rural disparities narrowed.

High value-added utilization of desulfurized building gypsum as self-leveling mortar: the comprehensive effect of cement.

The utilization of desulfurized building gypsum as raw material for gypsum-based self-leveling mortar (GSL) is limited by its low strength and poor water resistance. The objective of this study is to enhance comprehensive properties of GSL and prepare qualified desulfurized building gypsum-based self-leveling mortar that can be effectively applied in practical engineering projects. The influence of cement on water consumption rate of initial fluidity (W/M ratio), fluidity, setting time, mechanical strength, and water resistance of GSL were evaluated. Additionally, rheological parameter, heat of hydration, crystal morphology, and pore structure were also analyzed. Cement significantly improved the fluidity of slurry. Moreover, the compressive strength and softening coefficient of GSL reached 20.6 MPa and 0.56 at 10% cement, respectively. Furthermore, cement reduced the 30-min-fluidity loss and improved fludity by reducing the yield stress and increasing the plastic viscosity of screed. The transformation of hydration kinetics of GSL could be due to Ca2+ and OH- released by cement, thus resulting in the shortening of initial setting time and the prolongation of the interval between initial and final setting time. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) showed that CSH gel and AFt crystal would generate on the surface of CaSO4·2H2O crystal, making the structure more compact. Mercury intrusion porosimetry (MIP) indicated that cement greatly reduced the porosity through the water reduction effect in the early stage and continuous hydration in the later stage. The continuous hydration of cement also increased the shrinkage rate. This work was expected to provide reference for promoting the application of desulfurized building gypsum as the high value-added screed.

The underlying neuropsychological and neural correlates of the impaired Chinese reading skills in children with attention deficit hyperactivity disorder.

Impaired basic academic skills (e.g., word recognition) are common in children with Attention Deficit Hyperactivity Disorder (ADHD). The underlying neuropsychological and neural correlates of impaired Chinese reading skills in children with ADHD have not been substantially explored. Three hundred and two children with ADHD (all medication-naïve) and 105 healthy controls underwent the Chinese language skill assessment, and 175 also underwent fMRI scans (84 ADHD and 91 controls). Between-group and mediation analyses were applied to explore the interrelationships of the diagnosis of ADHD, cognitive dysfunction, and impaired reading skills. Five ADHD-related brain functional networks, including the default mode network (DMN) and the dorsal attention network (DAN), were built using predefined regions of interest. Voxel-based group-wise comparisons were performed. The ADHD group performed worse than the control group in word-level reading ability tests, with lower scores in Chinese character recognition (CR) and word chains (WS) (all P < 0.05). With full-scale IQ and sustained attention in the mediation model, the direct effect of ADHD status on the CR score became insignificant (P = 0.066). The underlying neural correlates for the orthographic knowledge (OT) and CR differed between the ADHD and the control group. The ADHD group tended to recruit more DMN regions to maintain their reading performance, while the control group seemed to utilize more DAN regions. Children with ADHD generally presented impaired word-level reading skills, which might be caused by impaired sustained attention and lower IQ. According to the brain functional results, we infer that ADHD children might utilize a different strategy to maintain their orthographic knowledge and character recognition performance.

Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein-Barr virus entry into epithelial cells.

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.

Diabetic Ocular Surface Has Defects in Oxygen Uptake Revealed by Optic Fiber Microsensor.

Purpose: Diabetes mellitus causes diabetic keratopathy (DK). This and other ocular surface disorders are underdiagnosed and problematic for affected patients as well as recipients of diabetic donor corneas. Thus, it is important to find noninvasive means to facilitate determination of the potentially vision-threatening DK. It has been reported that diabetic corneas uptake significantly less oxygen (O2) than healthy controls. However, an integral assessment of the ocular surface is missing. Methods: Using an optic-fiber O2 micro-sensor (optrode) we demonstrated recently that the healthy ocular surface displays a unique spatiotemporal map of O2 consumption. We hypothesize that diabetes impairs the spatiotemporal profile of O2 uptake at the ocular surface. Results: Using streptozotocin (STZ)-induced diabetic mice, we found diminished O2 uptake and loss of the unique pattern across the ocular surface. A diabetic cornea consumes significantly less O2 at the bulbar conjunctiva and limbus, but not the central and peripheral cornea, compared to controls. Further, we show that, contrary to the healthy cornea, the diabetic cornea does not increase the O2 consumption at the limbus in the evening as the normal control. Conclusions: Altogether, our measurements reveal a previously unknown impairment in O2 uptake at the diabetic cornea, making it a potential tool to diagnose ocular surface abnormalities and suggesting a new etiology mechanism.

Gene‒environment interaction effect of hypothalamic‒pituitary‒adrenal axis gene polymorphisms and job stress on the risk of sleep disturbances.

Background: Studies have shown that chronic exposure to job stress may increase the risk of sleep disturbances and that hypothalamic‒pituitary‒adrenal (HPA) axis gene polymorphisms may play an important role in the psychopathologic mechanisms of sleep disturbances. However, the interactions among job stress, gene polymorphisms and sleep disturbances have not been examined from the perspective of the HPA axis. This study aimed to know whether job stress is a risk factor for sleep disturbances and to further explore the effect of the HPA axis gene × job stress interaction on sleep disturbances among railway workers. Methods: In this cross-sectional study, 671 participants (363 males and 308 females) from the China Railway Fuzhou Branch were included. Sleep disturbances were evaluated with the Pittsburgh Sleep Quality Index (PSQI), and job stress was measured with the Effort-Reward Imbalance scale (ERI). Generalized multivariate dimensionality reduction (GMDR) models were used to assess gene‒environment interactions. Results: We found a significant positive correlation between job stress and sleep disturbances (P < 0.01). The FKBP5 rs1360780-T and rs4713916-A alleles and the CRHR1 rs110402-G allele were associated with increased sleep disturbance risk, with adjusted ORs (95% CIs) of 1.75 [1.38-2.22], 1.68 [1.30-2.18] and 1.43 [1.09-1.87], respectively. However, the FKBP5 rs9470080-T allele was a protective factor against sleep disturbances, with an OR (95% CI) of 0.65 [0.51-0.83]. GMDR analysis indicated that under job stress, individuals with the FKBP5 rs1368780-CT, rs4713916-GG, and rs9470080-CT genotypes and the CRHR1 rs110402-AA genotype had the greatest risk of sleep disturbances. Conclusions: Individuals carrying risk alleles who experience job stress may be at increased risk of sleep disturbances. These findings may provide new insights into stress-related sleep disturbances in occupational populations.

Solution Blow Spinning of the Benzimidazole-Containing Aramid Nanofibers for Separators of Lithium-Ion Batteries.

Nanofibers based on high-performance polymers are much highlighted in recent studies toward advanced lithium-ion batteries. Herein, we demonstrate one scalable poly(ethylene oxide) (PEO)-assisted solution blow spinning strategy for the preparation of heterocyclic aramid (HA) nanofibers of poly(p-phenylene-benzimidazole-terephthalamide). The incorporation of PEO is essential to improve the spinnability of the HA solution achieved directly through the low-temperature-solution copolymerization process. Additionally, the flexible PEO with a strong H-bonding affinity is also utilized as the molecular zipper to adjust the pore size of the nanofiber membrane during the post-treatment process. The obtained membrane combines the good wettability of PEO to the liquid electrolytes, with outstanding mechanical strength, modulus, toughness, and environmental resistance of HA. The nonwoven separator membranes with a porosity of 83.6% exhibited excellent comprehensive performance, which could be seen not only on the high tensile strength (68.2 MPa), modulus (3.0 GPa), and toughness but also on the high thermal stability (Td > 405 °C) and flame retardancy, as well as the high electrolyte uptake (302.4%). The ion conductivity of the porous separators reached 0.83 mS/cm, with the bulk resistance dropping to 1/4 of the reference polypropylene separator. In the assembly of the Li/LiFePO4 half battery, the HA separators displayed improved discharge specific capacity and high retention in both rate capability and cycling tests, providing the potential industrial preparation for advanced lithium-ion batteries.

World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Insufficient Sleep is Associated With Increasing Trends in Adolescent Suicidal Behaviors.

PURPOSE: Youth suicide has been increasing and became a public health concern worldwide. Identifying insufficient sleep as the potential risk factor is critical to reducing suicide risk and increasing trends. This study aimed to determine whether insufficient sleep is associated with increasing trends in suicidal behaviors and disparities by sex, age, and race/ethnicity among school adolescents. METHODS: The present study used biennial data from the US nationally representative Youth Risk Behavior Survey from 2007 to 2019. Joinpoint regression models were used to estimate biennial percent changes (BPCs) and average BPCs (ABPCs) of suicidal behaviors by sleep duration. Logistic regression models were used to examine the association between insufficient sleep and suicidal behaviors. RESULTS: Of 73,356 adolescent students included (mean [standard deviation] age, 16.11 [1.23] years), 50.03% were female. Suicidal ideation and suicide plan among insufficient sleep group increased from 2007 to 2019 (BPC = 2.88% [95% confidence interval {CI}: 1.65%, 4.13%]; BPC = 3.42% [95% CI: 2.09%, 4.77%]), but were nonsignificant among sufficient sleep group. Trends in suicidal ideation (ABPC = 3.03% [95% CI: 1.35%, 4.73%]) and suicide plan (ABPC = 4.03% [95% CI: 2.47%, 5.62%]) among female adolescents with insufficient sleep increased, but nonsignificant among male adolescents with insufficient sleep. Suicidal ideation (ABPC = 1.73% [95% CI: 0.51%, 2.97%]) and suicide plan (ABPC = 2.31% [95% CI: 0.70%, 3.95%]) increased among younger adolescents only with insufficient sleep, whereas suicide trends by sleep duration were similar among older adolescents. Suicide plan among insufficient sleep group increased across the four racial groups, with BPC highest for the White (BPC = 3.48% [95% CI: 1.31%, 5.69%]), and lowest for the Hispanic/Latino (BPC = 1.18% [95% CI: 0.15%, 2.23%]), but were nonsignificant among sufficient sleep group except for the White (BPC = 2.83% [95% CI: 0.62%, 5.09%]). DISCUSSION: Insufficient sleep was disproportionately associated with increasing trends in suicidal behaviors among female, younger, and non-White adolescent students. Ensuring sufficient sleep can potentially reduce suicide among school adolescents.

Designing a conjugate vaccine targeting Klebsiella pneumoniae ST258 and ST11.

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

Low-Toxicity Self-Photosensitized Biohybrid Systems for Enhanced Light-Driven H2 Production.

Nanoparticles (NPs) represent a potential optoelectronic source capable of significantly boosting hydrogen production; however, their inevitable cytotoxicity may lead to oxidative damage of bacterial cell membranes. In this study, we employed non-photosynthetic Escherichia coli K-12 as a model organism and utilized self-assembled cadmium sulfide (CdS) nanoparticles to construct a low-toxicity and hydrogen-production-enhancing self-photosensitive hybrid system. To mitigate the cytotoxicity of CdS NPs and synthesize biocompatible CdS NPs on the cell surface, we employed engineered E. coli (efeB/OE) for bioremediation, achieving this goal through the overexpression of the peroxidase enzyme (EfeB). A comparative analysis with E. coli-CdS revealed a significant downregulation of genes encoding oxidative stress proteins in efeB/OE-CdS post-irradiation. Atomic force microscopy (AFM) confirmed the stability of bacterial cell membranes. Due to the enhanced stability of the cell membrane, the hydrogen yield of the efeB/OE-CdS system increased by 1.3 times compared to the control, accompanied by a 49.1% reduction in malondialdehyde (MDA) content. This study proposes an effective strategy to alleviate the toxicity of mixed biological nanoparticle systems and efficiently harness optoelectronic electrons, thereby achieving higher hydrogen production in bioremediation.