Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort.

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

Biportal endoscopic paraspinal decompression for epidural cement leakage removal: A technical note.

OBJECTIVE: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy (UBE) for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS: The patient's postoperative clinical course was uneventful. CONCLUSIONS: A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.

Endoscopic management of recurrent obstructive jaundice after EUS-guided biliary drainage.

EUS-GUIDED biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. However, the risks of encountering recurrent biliary obstruction (RBO) after EUS-BD have increased due to the growing clinical experience of EUS-BD and prolonged prognosis of the underlying disease. Previous studies have shown that the incidence of RBO following EUS-BD ranges from 11% to 25%. Nevertheless, literature on the efficacy of reintervention of RBO after EUS-GUIDED hepaticogastrostomy (EUS-HGS) and case reports describing the procedural details of endoscopic reintervention following EUS-HGS are lacking.

Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Efficiency evaluation and promoter identification of primary health care system in China: an enhanced DEA-Tobit approach.

BACKGROUND: With Primary Health Care (PHC) being a cornerstone of accessible, affordable, and effective healthcare worldwide, its efficiency, especially in developing countries like China, is crucial for achieving Universal Health Coverage (UHC). This study evaluates the efficiency of PHC systems in a southwest China municipality post-healthcare reform, identifying factors influencing efficiency and proposing strategies for improvement. METHODS: Utilising a 10-year provincial panel dataset, this study employs an enhanced Data Envelopment Analysis (DEA) model integrating Slack-Based Measure (SBM) and Directional Distance Function (DDF) with the Global Malmquist-Luenberger (GML) index for efficiency evaluation. Tobit regression analysis identifies efficiency determinants within the context of China's healthcare reforms, focusing on horizontal integration, fiscal spending, urbanisation rates, and workforce optimisation. RESULTS: The study reveals a slight decline in PHC system efficiency across the municipality from 2009 to 2018. However, the highest-performing county achieved a 2.36% increase in Total Factor Productivity (TFP), demonstrating the potential of horizontal integration reforms and strategic fiscal investments in enhancing PHC efficiency. However, an increase in nurse density per 1,000 population negatively correlated with efficiency, indicating the need for a balanced approach to workforce expansion. CONCLUSIONS: Horizontal integration reforms, along with targeted fiscal inputs and urbanisation, are key to improving PHC efficiency in underdeveloped regions. The study underscores the importance of optimising workforce allocation and skillsets over mere expansion, providing valuable insights for policymakers aiming to strengthen PHC systems toward achieving UHC in China and similar contexts.

Dual-strategy engineered nickel phosphide for achieving efficient hydrazine-assisted hydrogen production in seawater.

Electrocatalytic hydrogen production in seawater to alleviate freshwater shortage pressures is promising, but is hindered by the sluggish oxygen evolution reaction and detrimental chloride electrochemistry. Herein, a dual strategy approach of Fe-doping and CeO2-decoration in nickel phosphide (Fe-Ni2P/CeO2) is rationally designed to achieve superior bifunctional catalytic performance for the hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR) in seawater. Notably, the two-electrode Fe-Ni2P/CeO2-based hybrid seawater electrolyzer realizes energy-efficient and chlorine-free hydrogen production with ultralow cell voltages of 0.051 and 0.597 V at 10 and 400 mA cm-2, which are significantly lower than those needed in the hydrazine-free seawater electrolyzer. Density functional theory calculations manifest that the combination of Fe doping and heterointerface construction between Fe-Ni2P and CeO2 can adjust the electronic structure of the Ni2P and optimize the water dissociation barrier and hydrogen adsorption free energy, leading to improvement of the intrinsic catalytic performance. This route affords a feasible solution for future large-scale hydrogen generation using abundant ocean water.

Effects of Hepatorenal Function on Urinary Alzheimer-Associated Neuronal Thread Protein: A Laboratory-Based Cross-Sectional Study Among the Older Chinese Population.

Background: Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is a biomarker for the early diagnosis of Alzheimer's disease (AD). It remains unclear whether hepatorenal function affects the urinary AD7c-NTP level. Objective: To evaluate the effects of hepatorenal function on urinary AD7c-NTP level. Methods: We enrolled 453 participants aged 60-100 years. An automated chemistry analyzer was used to determine the indicators of serum hepatorenal function. Enzyme-linked immunosorbent assay was used to measure the urinary AD7c-NTP level. Results: Spearman's correlation analysis showed a negative correlation between urinary AD7c-NTP levels and indicators of hepatorenal function, including albumin (r = -0.181, p < 0.001), albumin/globulin ratio (r = -0.224, p < 0.001), cholinesterase (r = -0.094, p = 0.046), total carbon dioxide (r = -0.102, p = 0.030), and glomerular filtration rate (r = -0.260, p < 0.001), as well as a positive correlation with globulin (r = 0.141, p = 0.003), aspartate transaminase (r = 0.186, p < 0.001), blood urine nitrogen (r = 0.210, p < 0.001), creatinine (r = 0.202, p < 0.001), uric acid (r = 0.229, p < 0.001), and cystatin C (r = 0.265, p < 0.001). The least absolute shrinkage and selection operator (LASSO) regression analysis and multiple linear regression model analyses showed that the statistically significant hepatorenal indicators for predicting AD7c-NTP were A/G (p = 0.007), AST (p = 0.002), BUN (p = 0.019), and UA (p = 0.003). Conclusions: The effects of hepatorenal indicators should be considered when using urinary AD7c-NTP levels in clinical settings.

Lipoprotein(a) and Diet: Consuming Sugar-Sweetened Beverages Lowers Lipoprotein(a) Levels in Obese and Overweight Adults.

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. A size polymorphism in the apolipoprotein(a) [apo(a)] gene, determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Non-genetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel-arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism. The mean (± SD) age of participants was 54 ± 8 years, 50% were women, and 75% were of European descent. At the end of the 10-week intervention, Lp(a) level was reduced by an average (± SEM) of -13.2% ± 4.3% in all participants (p=0.005); by -15.3% ± 7.8% in the 15 participants who consumed glucose (p=0.07); and by -11.3% ± 4.5% in the 17 participants who consumed fructose (p=0.02), without any significant difference in the effect between the two sugar groups. The relative changes in Lp(a) levels were similar across subgroups of lower vs higher baseline Lp(a) level or carrier vs non-carrier of an atherogenic small (≤22K) apo(a) size. In contrast, LDL-C increased. In conclusion, in older, overweight/obese adults, consuming sugar-sweetened beverages reduced Lp(a) levels by ∼13% independently of apo(a) size variability and the type of sugar consumed. The Lp(a) response was opposite to that of LDL-C and triglyceride concentrations. These findings suggest that metabolic pathways might impact Lp(a) levels.

Design of inductive electrostatic boom spray system based on embedded closed electrode structure and droplet distribution test in soybean field.

The large water demand, insufficient deposition on the back of the leaf and the uneven distribution of droplets are the problems of traditional agricultural ground plant protection machinery, which leads to low agricultural control efficiency. Combined with the advantages of electrostatic spray technology and the characteristics of high working efficiency and low probability of droplets drift of ground sprayer, an inductive electrostatic boom spray system based on embedded electrode structure is designed and mounted on a large self-propelled boom sprayer for field testing. Based on the working characteristics of the fan nozzle and the analysis of the theory of charge, the inductive electrostatic spray device is designed. The performance of the device is tested and the rationality of the system design is verified by COMSOL numerical simulations, charge-to-mass ratio, and particle size distribution measurements. The spray deposition scanning software and the Box-Behnken experimental design method are used to analyze the spray droplet deposition rate and coverage density of the sprayer on the front and back of the target leaves. The results show that the embedded closed electrode structure designed in this paper can avoid the problem of electrode wetting, and the electric field generated by it is mainly concentrated in the spray liquid film area, and the intensity reaches 6~7 V/m. At the conventional application height (500 mm), the maximum charge-to-mass ratio is 2.91 mC/kg, and the average particle size is 168.22 µm, which is 12.87% lower than that of ordinary spray, when the spray pressure is 0.3 MPa and the electrostatic voltage is 12 kV. The results of field experiments show that the optimum combination of the working parameters with the spray speed is 8.40 m/s, the spray pressure is 0.35 MPa, the charging voltage is 11.50 kV, the amount of droplet deposition in the lower dorsal area of the blade is 1.44 µL·cm-2. This study can provide a certain basis for the application of electrostatic spray technology in ground sprayers.

Mutual learning with memory for semi-supervised pest detection.

Effectively monitoring pest-infested areas by computer vision is essential in precision agriculture in order to minimize yield losses and create early scientific preventative solutions. However, the scale variation, complex background, and dense distribution of pests bring challenges to accurate detection when utilizing vision technology. Simultaneously, supervised learning-based object detection heavily depends on abundant labeled data, which poses practical difficulties. To overcome these obstacles, in this paper, we put forward innovative semi-supervised pest detection, PestTeacher. The framework effectively mitigates the issues of confirmation bias and instability among detection results across different iterations. To address the issue of leakage caused by the weak features of pests, we propose the Spatial-aware Multi-Resolution Feature Extraction (SMFE) module. Furthermore, we introduce a Region Proposal Network (RPN) module with a cascading architecture. This module is specifically designed to generate higher-quality anchors, which are crucial for accurate object detection. We evaluated the performance of our method on two datasets: the corn borer dataset and the Pest24 dataset. The corn borer dataset encompasses data from various corn growth cycles, while the Pest24 dataset is a large-scale, multi-pest image dataset consisting of 24 classes and 25k images. Experimental results demonstrate that the enhanced model achieves approximately 80% effectiveness with only 20% of the training set supervised in both the corn borer dataset and Pest24 dataset. Compared to the baseline model SoftTeacher, our model improves mAP @0.5 (mean Average Precision) at 7.3 compared to that of SoftTeacher at 4.6. This method offers theoretical research and technical references for automated pest identification and management.

Nonlinear dynamics of planetary roller screw mechanism.

The synchronous meshing of the gear pair and the screw pair is a typical feature of the planetary roller screw mechanism. In order to fully derive and analyze the nonlinear dynamic characteristics of the system, this paper creatively incorporates the time-varying meshing stiffness of gear pair and the comprehensive transmission error into the research content. Combined with the thread contact force and friction force between the roller and the screw and between the roller and the nut, the nonlinear dynamic model of the planetary roller screw mechanism considering the meshing excitation of the gear pair is established. According to the time domain diagram, frequency domain diagram, phase plane diagram, Poincaré section diagram, three-dimensional spectrum diagram, and spatial phase diagram, the nonlinear behavior of the system is described in detail, and the bifurcation evolution process of the system under the excitation frequency parameters of the external load is revealed. In addition, based on the theory of multi-scale method and considering the variables such as meshing stiffness, meshing damping, and load fluctuation, the stability equation of the primary resonance of the system is derived. The analysis of the stability of the system under different working conditions shows that the parameters are selected within a reasonable range, which effectively reduces the primary common amplitude value and enhances the overall stability of the system. The research content improves the previous system dynamics modeling method and provides a theoretical basis for the nonlinear dynamics modeling method and parameter optimization design of the planetary roller screw mechanism.

Isolation, whole genome sequencing and application of a broad-spectrum Salmonella phage.

Salmonella is considered as one of the most common zoonotic /foodborne pathogens in the world. The application of bacteriophages as novel antibacterial agents in food substrates has become an emerging strategy. Bacteriophages have the potential to control Salmonella contamination.We have isolated and characterized a broad-spectrum Salmonella phage, SP154, which can lyse 9 serotypes, including S. Enteritidis, S. Typhimurium, S. Pullorum, S. Arizonae, S. Dublin, S. Cholerasuis, S. Chester, S. 1, 4, [5], 12: i: -, and S. Derby, accounting for 81.9% of 144 isolates. SP154 showed a short latent period (40 min) and a high burst size (with the first rapid burst size at 107 PFUs/cell and the second rapid burst size at approximately 40 PFUs/cell). Furthermore, SP154 activity has higher survival rates across various environmental conditions, including pH 4.0-12.0 and temperatures ranging from 4 to 50 °C for 60 min, making it suitable for diverse food processing and storage applications. Significant reductions in live Salmonella were observed in different foods matrices such as milk and chicken meat, with a decrease of up to 1.9 log10 CFU/mL in milk contamination and a 1 log10 CFU/mL reduction in chicken meat. Whole genome sequencing analysis revealed that SP154 belongs to the genus Ithacavirus, subfamily Humphriesvirinae, within the family Schitoviridae. Phylogenetic analysis based on the terminase large subunit supported this classification, although an alternate tree using the tail spike protein gene suggested affiliation with the genus Kuttervirus, underscoring the limitations of relying on a single gene for phylogenetic inference. Importantly, no virulence or antibiotic resistance genes were detected in SP154. Our research highlights the potential of using SP154 for biocontrol of Salmonella in the food industry.

Animal Models of Chronic Migraine: From the Bench to Therapy.

PURPOSE OF REVIEW: Chronic migraine is a disabling progressive disorder without effective management approaches. Animal models have been developed and used in chronic migraine research. However, there are several problems with existing models. Therefore, we aimed to summarize and analyze existing animal models to facilitate translation from basic to clinical. RECENT FINDINGS: The most commonly used models are the inflammatory soup induction model and the nitric oxide donor induction model. In addition, KATP openers have also been used in model induction. Based on the above models, some molecular targets have been identified, such as glutamate receptors. However, each model has its shortcomings and characteristics, and there are still some common problems that need to be solved, such as spontaneous headache, evaluation criteria after model establishment, and identification methods. In this review, we summarized and highlighted the advantages and limitations of the currently commonly used animal models of chronic migraine with a special focus on drug discovery and current therapeutic strategies, and discussed the directions that can be worked on in the future.

Hydrogen sulfide enhances kiwifruit resistance to soft rot by regulating jasmonic acid signaling pathway.

As the third active gas signal molecule in plants, hydrogen sulfide (H2S) plays important roles in physiological metabolisms and biological process of fruits and vegetables during postharvest storage. In the present study, the effects of H2S on enhancing resistance against soft rot caused by Botryosphaeria dothidea and the involvement of jasmonic acid (JA) signaling pathway in kiwifruit during the storage were investigated. The results showed that 20 µL L-1 H2S fumigation restrained the disease incidence of B. dothidea-inoculated kiwifruit during storage, and delayed the decrease of firmness and the increase of soluble solids (SSC) content. H2S treatment increased the transcription levels of genes related to JA biosynthesis (AcLOX3, AcAOS, AcAOC2, and AcOPR) and signaling pathway (AcCOI1, AcJAZ5, AcMYC2, and AcERF1), as well as the JA accumulation. Meanwhile, H2S promoted the expression of defense-related genes (AcPPO, AcSOD, AcGLU, AcCHI, AcAPX, and AcCAT). Correlation analysis revealed that JA content was positively correlated with the expression levels of JA biosynthesis and defense-related genes. Overall, the results indicated that H2S could promote the increase of endogenous JA content and expression of defense-related genes by regulating the transcription levels of JA pathway-related genes, which contributed to the inhibition on the soft rot occurrence of kiwifruit.

Omics-based investigation on mechanisms controlling cellular internalization of keratin monomers during biodegradation by Stenotrophomonas maltophilia DHHJ.

INTRODUCTION: The global poultry industry produces millions of tons of waste feathers every year, which can be degraded to make feed, fertilizer, and daily chemicals. However, feather degradation is a complex process that is not yet fully understood. This results in low degradation efficiency and difficulty in industrial applications. Omics-driven system biology research offers an effective solution to quickly and comprehensively understand the molecules and mechanisms involved in a metabolic pathway. METHODS: In the early stage of this process, feathers are hydrolyzed into water-soluble keratin monomers. In this study, we used high-throughput RNA-seq technology to analyze the genes involved in the internalization and degradation of keratin monomers in S. maltophilia DHHJ strain cells. Moreover, we used Co-IP with LC-MS/MS technology to search for proteins that interact with recombinant keratin monomers. RESULTS: We discovered TonB transports and molecular chaperones associating with the keratin monomer, which may play a crucial role in the transmembrane transport of keratin. Meanwhile, multiple proteases belonging to distinct families were identified as binding partners of keratin monomers, among which ATPases associated with diverse cellular activities (AAA+) family proteases are overrepresented. Four genes, including JJL50_15620, JJL50_17955 (TonB-dependent receptors), JJL50_03260 (ABC transporter ATP-binding protein), and JJL50_20035 (ABC transporter substrate-binding protein), were selected as representatives for determining their expressions under different culture conditions using qRT-PCR and they were found to be upregulated in response to keratin degradation consistent with the data from RNA-seq and Co-IP. CONCLUSION: This study highlights the complexity of keratin biodegradation in S. maltophilia DHHJ, in which multiple pathways are involved such as protein folding, protein transport, and several protease systems. Our findings provide new insights into the mechanism of feather degradation.

Identifying behaviour-related and physiological risk factors for suicide attempts in the UK Biobank.

Suicide is a global public health challenge, yet considerable uncertainty remains regarding the associations of both behaviour-related and physiological factors with suicide attempts (SA). Here we first estimated polygenic risk scores (PRS) for SA in 334,706 UK Biobank participants and conducted phenome-wide association analyses considering 2,291 factors. We identified 246 (63.07%) behaviour-related and 200 (10.41%, encompassing neuroimaging, blood and metabolic biomarkers, and proteins) physiological factors significantly associated with SA-PRS, with robust associations observed in lifestyle factors and mental health. Further case-control analyses involving 3,558 SA cases and 149,976 controls mirrored behaviour-related associations observed with SA-PRS. Moreover, Mendelian randomization analyses supported a potential causal effect of liability to 58 factors on SA, such as age at first intercourse, neuroticism, smoking, overall health rating and depression. Notably, machine-learning classification models based on behaviour-related factors exhibited high discriminative accuracy in distinguishing those with and without SA (area under the receiver operating characteristic curve 0.909 ± 0.006). This study provides comprehensive insights into diverse risk factors for SA, shedding light on potential avenues for targeted prevention and intervention strategies.

Isolation of camel single domain antibodies against Yersinia pestis V270 antigen based on a semi-synthetic single domain antibody library and development of a VHH-based lateral flow assay.

BACKGROUND: Antibodies have been proven effective as diagnostic agents for detecting zoonotic diseases. The variable domain of camel heavy chain antibody (VHH), as an antibody derivative, may be used as an alternative for traditional antibodies in existing immunodiagnostic reagents for detecting rapidly spreading infectious diseases. OBJECTIVES: To expedite the isolation of specific antibodies for diagnostic purposes, we constructed a semi-synthetic camel single domain antibody library based on the phage display technique platform (PDT) and verified the validity of this study. METHODS: The semi-synthetic single domain antibody sequences consist of two parts: one is the FR1-FR3 region amplified by RT-PCR from healthy camel peripheral blood lymphocytes (PBLs), and the other part is the CDR3-FR4 region synthesised as an oligonucleotide containing CDR3 randomised region. The two parts were fused by overlapping PCR, resulting in the rearranged variable domain of heavy-chain antibodies (VHHs). Y. pestis low-calcium response V protein (LcrV) is an optional biomarker to detect the Y. pestis infection. The semi-synthetic library herein was screened using recombinant (LcrV) as a target antigen. RESULTS: After four cycles of panning the library, four VHH binders targeting 1-270 aa residues of LcrV were isolated. The four VHH genes with unique sequences were recloned into an expression vector and expressed as VHH-hFc chimeric antibodies. The purified antibodies were identified and used to develop a lateral flow immunoassay (LFA) test strip using latex microspheres (LM) for the rapid and visual detection of Y. pestis infection. CONCLUSIONS: These data demonstrate the great potential of the semi-synthetic library for use in isolation of antigen-specific nanobodies and the isolated specific VHHs can be used in antigen-capture immunoassays.

High bioavailable testosterone levels increase the incidence of isolated REM sleep behavior disorder: Results from multivariable and network Mendelian randomization analysis.

OBJECTIVES: To explore the causal relationships between sex hormone levels and incidence of isolated REM sleep behavior disorder (iRBD). METHODS: In our study, we utilized Genome-Wide Association Studies (GWAS) data for iRBD, including 9447 samples with 1061 cases of iRBD provided by the International RBD Study Group. Initially, we conducted a two-sample univariate MR analysis to explore the impact of sex hormone-related indicators on iRBD. This was followed by the application of multivariable MR methods to adjust for other hormone levels and potential confounders. Finally, we undertook a network MR analysis, employing brain structure Magnetic Resonance Imaging (MRI) characteristics as potential mediators, to examine whether sex hormones could indirectly influence the incidence of iRBD by affecting brain structure. RESULTS: Bioavailable testosterone (BioT) is an independent risk factor for iRBD (Odds Ratio [95 % Confidence Interval] = 2.437 [1.308, 4.539], P = 0.005, corrected-P = 0.020), a finding that remained consistent even after adjusting for other sex hormone levels and potential confounders. Additionally, BioT appears to indirectly increase the risk of iRBD by reducing axial diffusivity and increasing the orientation dispersion index in the left cingulum and cingulate gyrus. CONCLUSIONS: Our research reveals that elevated levels of BioT contribute to the development of iRBD. However, the specific impact of BioT on different sexes remains unclear. Furthermore, high BioT may indirectly lead to iRBD by impairing normal pathways in the left cingulum and cingulate gyrus and fostering abnormal pathway formation.