Characterizing the impact of reservoir storage and discharge on nitrogen dynamics in an upstream wetland using a δ15N and δ18O dual-isotope approach.

The identification of nitrate sources in reservoir water is important for watershed-scale surface pollution management. Significant fluctuations in river water levels arising from reservoir storage and discharge influence nitrate sources and transport processes. The Sanmenxia Reservoir, in the middle reaches of the Yellow River in China, undergoes significant water level changes (290-316 m), altering the composition of the nitrogen sources. This study employed a δ15N and δ18O dual-isotope method and MixSIAR modeling to quantify the contributions of nitrate sources. This reveals the impact of reservoir water impoundment and discharge on nitrogen dynamics in the upstream region of the wetland and the model sensitivity for each nitrate source. The results showed that the average concentrations of nitrate­nitrogen (NO- 3-N) were elevated during the impoundment period compared to the discharge period. Nitrogen sources exhibited varying proportions in surface water, groundwater, and soil water during both the impoundment and discharge periods. The predominant sources include manure and sewage (MS), with a maximum proportion of 57.4 % in surface water. Soil nitrogen (SN) accounted for 25.8 % of groundwater nitrogen and 32.1 % of soil water nitrogen during the impoundment period, whereas, during the discharge period, soil nitrogen made up 41.4 % of surface water nitrogen, manure and sewage contributed 44.8 % of groundwater nitrogen, and manure and sewage dominated with 56.7 % of soil water nitrogen. Sensitivity analysis of the MixSIAR model revealed that the isotopic composition of the manure and sewage primary source most significantly influenced the apportionment results of the riverine nitrate source. Reservoir discharge facilitates the dissimilatory nitrate reduction to ammonium (DNRA). The migration of NO- 3 from surface water to soil water and groundwater occurred from the impoundment period to the discharge period.

Lifestyle factors, glycemic traits, and lipoprotein traits and risk of liver cancer: a Mendelian randomization analysis.

The current state of knowledge on the relationship between lifestyle factors, glycemic traits, lipoprotein traits with liver cancer risk is still uncertain despite some attempts made by observational studies. This study aims to investigate the causal genetic relationship between factors highly associated with liver cancer incidence by using Mendelian randomization (MR) analysis. Employing MR analysis, this study utilized previously published GWAS datasets to investigate whether lifestyle factors, glycemic traits, and lipoprotein traits would affect the risk of liver cancer. The study utilized three MR methods, including inverse variance-weighted model (IVW), MR Egger, and weighted median. Furthermore, MR-Egger analyses were performed to detect heterogeneity in the MR results. The study also conducted a leave-one-out analysis to assess the potential influence of individual SNPs on the MR analysis results. MR-PRESSO was used to identify and remove SNP outliers associated with liver cancer. MR analyses revealed that 2-h glucose (odds ratio, OR 2.33, 95% confidence interval, CI 1.28-4.21), type 2 diabetes mellitus (T2DM, OR 1.67, 95% CI 1.18-2.37), body mass index (BMI, OR 1.67, 95% CI 1.18-2.37), waist circumference (OR 1.78, 95% CI 1.18-2.37) were associated with increased risk of liver cancer. On the contrary, apolipoproteins B (APOB, OR 0.67, 95% CI 0.47-0.97), and low-density lipoprotein (LDL, OR 0.62, 95% CI 0.42-0.92) were negatively related to liver cancer risk. Additionally, after adjusting for BMI, apolipoproteins A-I (APOA-I, OR 0.56, 95% CI, 0.38-0.81), total cholesterol (TC, OR 0.72, 95% CI, 0.54-0.94), and total triglycerides (TG, OR 0.57, 95% CI, 0.40-0.78) exhibited a significant inverse correlation with the risk of liver cancer. This study supports a causal relationship between 2-h glucose, T2DM, BMI, and waist circumference with the increased risk of liver cancer. Conversely, the study reveals a cause-effect relationship between TC, TG, LDL, APOA-I, and APOB with a decreased risk of liver cancer.

Interaction of different chloro-substituted phenylurea herbicides (diuron and chlortoluron) with bovine serum albumin: Insights from multispectral study.

In this work, the interaction between different chloro-substituted phenylurea herbicides (diuron (DIU) and chlortoluron (CHL)) and BSA were investigated and compared at three different temperatures (283 K, 298 K and 310 K) adopting UV-vis, fluorescence, and circular dichroism spectra. The quenching mechanism of the interaction was also proposed. The energy transfer between BSA and DIU/CHL was investigated. The binding sites of DIU/CHL and BSA and the variations in the microenvironment of amino acid residues were studied. The changes of the secondary structure of BSA were analyzed. The results indicate that both DIU and CHL can significantly interact with BSA, and the degree of the interaction between DIU/CHL and BSA increases with the increase of the DIU/CHL concentration. The fluorescence quenching of BSA by DIU/CHL results from the combination of static and dynamic quenching. The DIU/CHL has a weak to moderate binding affinity for BSA, and the binding stoichiometry is 1:1. Their binding processes are spontaneous, and hydrophobic interaction, hydrogen bonds and van der Waals forces are the main interaction forces. DIU/CHL has higher affinity for subdomain IIA (Site I) of BSA than subdomain IIIA (Site II), and also interacts with tryptophan more than tyrosine residues. The energy transfer can occur from BSA to DIU/CHL. By comparison, the strength of the interaction of DIU-BSA is always greater than that of CHL-BSA, and DIU can destroy the secondary structure of BSA molecules greater than CHL and thus the potential toxicity of DIU is higher due to DIU with more chlorine substituents than CHL. It is expected that this study on the interaction can offer in-depth insights into the toxicity of phenylurea herbicides, as well as their impact on human and animal health at the molecular level.

Efficient Poly-Adenine-Tailed DNA Functionalization of Gold Nanorods for Tailored Nanostructure Assembly.

Gold nanorods (AuNRs) with unique optical properties play a pivotal role in applications in plasmonic imaging, small molecule detection, and photothermal therapy. However, challenges in DNA functionalization of AuNRs hinder their full potential due to the presence of a dense cetyltrimethylammonium bromide (CTAB) bilayer, impeding close DNA contact. In this study, we introduced a convenient approach for the rapid assembly of polyadenine (polyA) tailed DNA on AuNRs with control of DNA density, rigidity, and valence. We explored the impact of DNA with designed properties on the construction of core-satellite structures by employing AuNRs as cores and spherical gold nanoparticles (AuNSs) as satellites. Density, rigidity, and valence are identified as crucial factors for efficient construction. Specifically, polyA-tailed DNA modulated DNA density and reduced spatial hindrance and electrostatic repulsion, thereby facilitating the construction. Enhancing the rigidity of DNA and incorporating multiple binding sites can further improve the efficiency.

Insights into interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin via multi-spectral analysis.

In this study, the interaction of triazine herbicides with three kinds of different alkyl groups (simetryne, ametryn and terbutryn) with human serum albumin (HSA) are investigated through UV-vis, fluorescence, and circular dichroism (CD) spectra. The mechanisms on the fluorescence quenching of HSA initiated by triazine herbicides are obtained using Stern-Volmer, Lineweaver-Burk and Double logarithm equations. The quenching rate constant (Kq), Stern-Volmer quenching constant (Ksv), binding constant (KA), thermodynamic parameters such as enthalpy change (∆H), entropy change (∆S) and Gibbs free energy (∆G) and number of binding site (n) are calculated and compared. The variations in the microenvironment of amino acid residues are studied by synchronous fluorescence spectroscopy. The binding sites and subdomains are identified using warfarin and ibuprofen as site probes. The conformational changes of HSA are measured using CD spectra. The results reveal that the triazine herbicides with different alkyl groups can interact with HSA by static quenching. The combination of the three herbicides and HSA are equally proportional, and the binding processes are spontaneous. Hydrophobic interaction forces play important roles in simetryne-HSA and ametryn-HSA, while the interaction of terbutryn-HSA is Van der Waals forces and hydrogen bonding. Moreover, the three herbicides can bind to HSA at site I (sub-domain IIA) more than site II (subdomain IIIA), and combine with tryptophan (Trp) more easily than tyrosine (Tyr) residues, respectively. By comparison, the order of interaction strength is terbutryn-HSA > ametryn-HSA > simetryne-HSA. Terbutryn can destroy the secondary structure of HSA more than simetryne and ametryn, and the potential toxicity of terbutryn is higher. It is expected that the interactions of triazine herbicides with HSA via multi-spectral analysis can offer some valuable information for studying the toxicity and the harm of triazine herbicides on human health at molecular level in life science.

NF2 is a candidate diagnosis, prognostic, and immunotherapeutic biomarker: a systematic pan-cancer analysis.

Background: Neurofibromin 2 (NF2) regulates diverse cellular events such as transcription, translation, ubiquitination, and micro-RNA biosynthesis. Previous evidence revealed that aberrant expression of NF2 contributes to tumorigenesis in mesothelioma, meningioma, and breast cancer. However, there is no comprehensive pan-cancer analysis to explore NF2's function in cancer diagnosis, prognosis, and immunological prediction. Methods: By extensive use of data profiles from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) project, Cancer Cell Line Encyclopedia (CCLE), CIBERSORT, Human Protein Atlas (HPA), and cBioPortal, we employed various bioinformatics methods to explore the role of NF2 in pan-cancer, including analyzing the association between NF2 and tumor diagnosis, prognosis, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the co-expression relationship between NF2 expression with RNA modification genes was also constructed. Results: Our research indicated that NF2 was highly expressed in most kinds of tumors. NF2 showed an early diagnosis value in 13 types of tumors and was significantly associated with the prognosis in most tumors. The results also verified that NF2 expression was associated with most immune-related cells and signaling pathways in pan-cancer, especially in diffuse large B-cell lymphoma and ovarian serous cystadenocarcinoma. Furthermore, NF2 gene expression was associated with TMB and MSI in many tumors. Conclusions: Our study reveals that NF2 might be helpful in tumor early diagnosis and prognosis evaluation. The expression of NF2 is highly associated with the tumor immune microenvironment. Additionally, NF2 is a potential biomarker for predicting the efficacy of immune checkpoint inhibitors therapy. Therefore, NF2 can be a promising diagnostic, prognostic, and immunotherapeutic biomarker for many types of tumors.

Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China: Evidence from a prospective cohort study.

BACKGROUND: Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear. METHODS: The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference. RESULTS: A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories. CONCLUSIONS: The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

Temporal trends in mortality of tuberculosis attributable to high fasting plasma glucose in China from 1990 to 2019: a joinpoint regression and age-period-cohort analysis.

Background: Nowadays, high fasting plasma glucose (HFPG) has been identified as the important risk factor contributing to the increased burden of diseases. But there remains a lack of research on tuberculosis (TB) mortality specifically attributable to HFPG. Thus, this study aims to explore the long-term trends in HFPG-related TB mortality in China from 1990 to 2019. Methods: Data on HFPG-related TB mortality were obtained from the Global Burden of Disease (GBD) Study 2019. Analyzing the data using joinpoint regression and age-period-cohort methods adjusting for age, period, and cohort allowed us to assess the trends in TB mortality due to HFPG. Results: The age-standardized mortality rates (ASMRs) of TB attributable to HFPG exhibited a downward trend in China from 1990 to 2019, with an average annual percentage change (AAPC) of -7.0 (95% CI, -7.5 to -6.6). Similar trends were found for male (AAPC of -6.5 [95% CI, -7.0 to -6.0]) and female (AAPC of -8.2 [95% CI, -8.5 to -7.9]), respectively. Local drifts curve with a U-shaped pattern reflected the AAPC of TB mortality due to HFPG across age groups. The greatest decline was observed in the age group of 60-64 years. The mortality rates related to HFPG first increased and then decreased with increasing age, peaking in the 55-59 age group. Our analysis of the period and cohort effects found that the rate ratios of TB mortality due to HFPG have decreased over the past three decades, more prominently in women. It is noteworthy that while both genders have seen a decline in HFPG-attributable TB mortality and risk, men have a higher risk and slightly less significant decline than women. Conclusion: The present study shows that HFPG-related ASMRs and risk of TB in China decreased over the last 30 years, with similar trends observed in both men and women. In order to attain the recommended level set by the WHO, the effective strategies for glycemic control and management still needed to be implemented strictly to further decrease the burden of TB.

Morphology Dictated Immune Activation with Framework Nucleic Acids.

Framework nucleic acids (FNAs) of various morphologies, designed using the precise and programmable Watson-Crick base pairing, serve as carriers for biomolecule delivery in biology and biomedicine. However, the impact of their shape, size, concentration, and the spatial presentation of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) on immune activation remains incompletely understood. In this study, representative FNAs with varying morphologies are synthesized to explore their immunological responses. Low concentrations (50 nM) of all FNAs elicited no immunostimulation, while high concentrations of elongated DNA nanostrings and tetrahedrons triggered strong activation due to their larger size and increased cellular uptake, indicating that the innate immune responses of FNAs depend on both dose and morphology. Notably, CpG ODNs' immune response can be programmed by FNAs through regulating the spatial distance, with optimal spacing of 7-8 nm eliciting the highest immunostimulation. These findings demonstrate FNAs' potential as a designable tool to study nucleic acid morphology's impact on biological responses and provide a strategy for future CpG-mediated immune activation carrier design.

Single-Molecule Nanomechanical Genotyping with DNA Origami-Based Shape IDs.

Atomic force microscopy (AFM)-based nanomechanical imaging provides a sub-10-nm-resolution approach for imaging biomolecules under ambient conditions. Here we describe how to generate a set of DNA origami-based shape IDs (triangular and cross shape, with and without streptavidin) to site-specifically label target genomic DNA sequences containing two single-nucleotide polymorphisms (SNPs). Adjacent labeling sites separated by only 30 nucleobases (~10 nm) can be differentiated under AFM imaging. We can directly genotype single molecules of human genomic DNA.

The risk of acute and early HIV (AEH) infection among MSM with different behaviour trajectories: an open cohort study in Tianjin, China, 2011-2019.

BACKGROUND: Acute and early HIV (AEH) infection is characterized by a high viral load and infectivity. Approximately 50% of cases of HIV-1 transmission occur during AEH. Understanding sexual behaviour trajectories would be useful for predicting changes in the risk of HIV acquisition. However, few studies have investigated sexual behaviour trajectories and their association with AEH acquisition. This study identified behaviour trajectories among men who have sex with men (MSM), determined the risk of AEH infection, and compared risk factors between different behaviour trajectories. METHODS: The study was based on an ongoing prospective open cohort of voluntary HIV counselling and testing (VHCT) among MSM in Tianjin, China. From 2011 to 2019, 1974 MSM were recruited. Group-based trajectory modelling (GBTM) was used to identify behaviour trajectories by constructing a sexual risk behaviour score. Logistic regression and generalized estimating equation (GEE) were used to compare the risk of AEH infection and risk factors for different behaviour trajectories. All data analyses were performed using SAS 9.4. RESULTS: The incidence of AEH infection was 1.76/100 person-years, with 64 AEH infections documented in 3633 person-years of follow-up. Three sexual behaviour trajectories were identified: CL (consistently low risk, 35.46%), CH (consistently high risk, 42.71%) and HTL (high to low risk, 21.83%). MSM in the HTL and CH groups had higher AEH infection rates than MSM in the CL group (6.73%, 3.08% and 1.28%, respectively), with ORs of 5.54 (2.60, 11.82) and 2.44 (1.14, 5.25), respectively. MSM aged 30-50 years old and MSM who underwent HIV testing in the last year were more likely to be in the CH group and HTL group. In addition, the HTL group was characterized by a lower likelihood of local registration and a higher likelihood of working as a MSW. CONCLUSION: MSM in the CH group and the HTL group had a higher risk of AEH infection. In the future, VHCT should be performed more often among younger MSM, and HIV counselling should be given the same priority as HIV testing. In addition, VHCT combined with PrEP may have a better preventive impact on MSM with a high risk of AEH infection.

Imaging tools for plant nanobiotechnology.

The successful application of nanobiotechnology in biomedicine has greatly changed the traditional way of diagnosis and treating of disease, and is promising for revolutionizing the traditional plant nanobiotechnology. Over the past few years, nanobiotechnology has increasingly expanded into plant research area. Nanomaterials can be designed as vectors for targeted delivery and controlled release of fertilizers, pesticides, herbicides, nucleotides, proteins, etc. Interestingly, nanomaterials with unique physical and chemical properties can directly affect plant growth and development; improve plant resistance to disease and stress; design as sensors in plant biology; and even be used for plant genetic engineering. Similarly, there have been concerns about the potential biological toxicity of nanomaterials. Selecting appropriate characterization methods will help understand how nanomaterials interact with plants and promote advances in plant nanobiotechnology. However, there are relatively few reviews of tools for characterizing nanomaterials in plant nanobiotechnology. In this review, we present relevant imaging tools that have been used in plant nanobiotechnology to monitor nanomaterial migration, interaction with and internalization into plants at three-dimensional lengths. Including: 1) Migration of nanomaterial into plant organs 2) Penetration of nanomaterial into plant tissues (iii)Internalization of nanomaterials by plant cells and interactions with plant subcellular structures. We compare the advantages and disadvantages of current characterization tools and propose future optimal characterization methods for plant nanobiotechnology.

Sexual behaviour changes and HIV infection among men who have sex with men: evidence from an open cohort in China.

BACKGROUND: The HIV epidemic in key populations such as men who have sex with men (MSM) is a public health issue of worldwide concern. China has seen an increase in newly diagnosed HIV infections through male-male sexual contact in the past decade. In a long-term cohort, how the complex behaviour pattern of MSM changed and the association with the HIV risk are unclear at present. METHODS: This study was conducted from October 2011 to December 2019 in Tianjin. MSM were recruited by snowball sampling through online and offline ways. Demographic and sexual behavioural data were collected for analysis. Three indicators (condom use in last anal sex, frequency of condom use during anal sex and the number of sexual partners) were used to define the behaviour change. Participants with zero, one, and two or three risk indicators were categorised into behaviour types of 'protective', 'moderate', and 'fragile', respectively. Change in behaviour type between baseline and each visit was considered. Time-varying Cox models were performed to evaluate HIV infection risk. RESULTS: Of 2029 MSM included in the study, 127 were new HIV diagnoses. The overall incidence rate was 3.36 per 100 person-years. The percentage of 'protective' and 'moderate' behaviour types had a conspicuous growth trend as the follow-up. Furthermore, the HIV incidence rate in each visit among different behaviour transition types showed a general downward trend as the number of total follow-up times increased. Individuals who remained in 'fragile' (adjusted HR (aHR): 25.86, 95% CI: 6.92 to 96.57) or changed from 'protective' to 'moderate' (aHR: 4.79, 95% CI: 1.18 to 19.47), 'protective' to 'fragile' (aHR: 23.03, 95% CI: 6.02 to 88.13), and 'moderate' to 'fragile' (aHR: 25.48, 95% CI: 6.79 to 95.40) between baseline and the last follow-up had a higher HIV risk. Gained risk indicators were associated with the increase of HIV risk (gained one indicator, aHR: 2.67, 95% CI: 1.68 to 4.24; gained two or three indicators, aHR: 4.99, 95% CI: 3.00 to 8.31) while losing just one risk indicator could halve the risk (aHR: 0.43, 95% CI: 0.21 to 0.90). CONCLUSIONS: Among MSM in Tianjin, it is necessary to get timely behaviour change for those with high-incidence behaviour patterns while sustaining for those with low-incidence patterns. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2000039500).

Sexual Behavior Transition and Acute and Early HIV Infection Among Men Who Have Sex With Men: Evidence from an Open Cohort in China, 2011-2019.

The present study examined how sexual behaviors transit over time among men who have sex with men (MSM) and whether these transitions were associated with acute and early HIV (AEH) infection. An open cohort study was conducted using snowball sampling to recruit MSM via physical venues and Internet venues from 2011 to 2019, in China. Cox models were used to estimate the correlates of risk factors and AEH infection. We used Latent Transition Analysis (LTA) to describe behavioral profile and explore latent behavioral "trans-phenotypes," then examined the effect between different "trans-phenotypes" and AEH infection risk and explored the effect of characteristics as possible predictors of sexual behavior transition. Of 6502 MSM, a total of 1974 individuals with negative human immunodeficiency virus (HIV) tests at baseline and at least 2 visit records were included in the final analysis from 2011 to 2019. During an average 1.84 years of follow-up, 64 AEH infections were documented. In the multivariable Cox model, the association between condom use in last anal sex (HR: 0.095, 0.038-0.205), fewer sexual partners (HR: 0.375, 0.205-0.712), low frequency of condom use (HR: 3.592, 1.186-11.272), and AEH acquisition were found. The percentage of MSM with "maintain/develop safety-profile," "consistent risky-profile," and "safety-profile to risky-profile" were 52.48, 40.17, and 7.35%, respectively. Compared with "maintain\develop safety-profile," "consistent or develop risky-profile" had an increasing likelihood of AEH infection. Meanwhile, male sex workers (MSWs) or older MSM were more likely to consist or transit in "risky-profile." Having middle education is a risk factor to transit in "risky-profile" for MSM with "safety-profile" at baseline. In addition, MSM who accept health services in the past year engaged in higher proportion of developing safety-profile. Approximately half of MSM maintain or develop risky behavior with the increasing likelihood of AEH acquisition in China, which suggested that targeted and intensive interventions should be prioritized to maintain safety-profile. Clinical Trial Number: ChiCTR2000039500.

Effects of daily mean temperature and other meteorological variables on bacillary dysentery in Beijing-Tianjin-Hebei region, China.

BACKGROUND: Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution. METHODS: Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM. RESULTS: A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates. CONCLUSIONS: This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.

The Effect of the Nanoparticle Shape on T Cell Activation.

The mechanism of extracellular ligand nano-geometry in ex vivo T cell activation for immunotherapy remains elusive. Herein, the authors demonstrate large aspect ratio (AR) of gold nanorods (AuNRs) conjugated on cell culture substrate enhancing both murine and human T cell activation through the nanoscale anisotropic presentation of stimulatory ligands (anti-CD3(αCD3) and anti-CD28(αCD28) antibodies). AuNRs with large AR bearing αCD3 and αCD28 antibodies significantly promote T cell expansion and key cytokine secretion including interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). High membrane tension observed in large AR AuNRs regulates actin filament and focal adhesion assembly and develops maturation-related morphological features in T cells such as membrane ruffle formation, cell spreading, and large T cell receptor (TCR) cluster formation. Anisotropic stimulatory ligand presentation promotes differentiation of naïve CD8+ T cells toward the effector phenotype inducing CD137 expression upon co-culture with human cervical carcinoma. The findings suggest the importance of manipulating extracellular ligand nano-geometry in optimizing T cell behaviors to enhance therapeutic outcomes.

Biomaterial-mediated presentation of wnt5a mimetic ligands enhances chondrogenesis and metabolism of stem cells by activating non-canonical Wnt signaling.

The presentation of development-relevant bioactive cues by biomaterial scaffolds is essential to the guided differentiation of seeded human mesenchymal stem cells (hMSCs) and subsequent tissue regeneration. Wnt5a is a critical non-canonical Wnt signaling ligand and plays a key role in the development of musculoskeletal tissues including cartilage. Herein we investigate the efficacy of biofunctionalizing the hyaluronic acid hydrogel with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the chondrogenesis of hMSCs and the potential underlying molecular mechanism. Our findings show that the conjugation of Foxy5 peptide in the hydrogels activates non-canonical Wnt signaling of encapsulated hMSCs via the upregulation expression of PLCE1, CaMKII-ß, and downstream NFATc1, leading to enhanced expression of chondrogenic markers such as SOX9. The decoration of Foxy5 peptide also promotes the metabolic activities of encapsulated hMSCs as evidenced by upregulated gene expression of mitochondrial complex components and glucose metabolism biomarkers, leading to enhanced ATP biosynthesis. Furthermore, the conjugation of Foxy5 peptide activates the non-canonical Wnt, PI3K-PDK-AKT and IKK/NF-κB signaling pathways, thereby inhibiting the hypertrophy of the chondrogenically induced hMSCs in the hydrogels under both in vitro and in vivo conditions. This enhanced chondrogenesis and attenuated hypertrophy of hMSCs by the biomaterial-mediated bioactive cue presentation facilitates the potential clinical translation of hMSCs for cartilage regeneration. Our work provides valuable guidance to the rational design of bio-inductive scaffolds for various applications in regenerative medicine.

Clinical use of HD-MTX monotherapy in a rare case of refractory primary bone diffuse large B-cell lymphoma with long-term survival after local radiotherapy: A case report.

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) has been rarely reported because of its low incidence. The optimal treatment plan for patients with relapsed/refractory PB-DLBCL remains controversial. In this study, we present a case of a 57-year-old patient with refractory PB-DLBCL to better understand this disease. The patient developed lumbosacral/low extremity pain. A lumbar magnetic resonance imaging (MRI) revealed skeletal lesions with osteolysis in L4-L5 and S1. With the failure of multi-line chemotherapy, the patient developed paralysis of both lower limbs. 18-Fluorinefluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and MRI showed new lesions in the femoral head, cervical and thoracic vertebrae. We tried to treat the patient with adjuvant radiotherapy and 10 courses of high-dose methotrexate (HD-MTX)-based monotherapy, after which the patient was able to walk and achieved complete remission (CR). To the best of our knowledge, this is the first attempt to use local radiotherapy combined with an HD-MTX regimen successfully for the treatment of refractory PB-DLBCL.

Nanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy.

A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired.

Low awareness of and willingness to use PrEP in the Chinese YMSM: An alert in YMSM HIV prevention.

OBJECTIVES: Despite being a key population in whom to initiate pre-exposure prophylaxis (PrEP), the awareness of and willingness to use PrEP are still unclear in Chinese young men who have sex with men (YMSM). We report factors associated with PrEP awareness and willingness in the population. METHODS: From 1 August to 31 December 2018, 495 participants aged 15-24 years were included in a cross-sectional study about awareness of and willingness to use PrEP among YMSM. Logistic regression models were used to identify factors associated with two outcomes: awareness of PrEP; and willingness to use PrEP. RESULTS: Among 495 eligible participants, 129 participants (26.1%) knew about PrEP. PrEP awareness among YMSM was associated with higher education level [adjusted odds ratio (aOR) = 1.812, 95% CI: 1.113-2.951] and previous HIV testing (aOR = 3.507, 95% CI: 1.261-9.752). YMSM with shorter local residence time (aOR = 0.317, 95% CI: 0.101-0.992) and internet-based partner-seeking (aOR = 0.171, 95% CI: 0.096-0.305) were less likely to be aware of PrEP. In those with previous knowledge of PrEP, 36 (27.9%) conveyed their willingness to use it. PrEP willingness was associated with internet-based partner-seeking (aOR = 9.593, 95% CI: 1.965-46.844). The main barriers influencing those who knew about PrEP but refused to use it were the high price of PrEP (69.9%), the need to use condoms consistently (52.7%), and concerns about side effects (39.8%) and effectiveness of prevention (22.6%). CONCLUSIONS: Chinese YMSM have low awareness of and willingness to use PrEP. Adequate PrEP promotions should be implemented, especially on the Internet and dating software.