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Cervical carcinoma is the second most common cancer in women worldwide with greater than 99% of the cases caused by human papillomaviruses (HPVs). Early detection of HPVs especially the high risk types (HR-HPVs) are essential to prevent the disease progression. The existing methods for HPV detection, such as qPCR are of high sensitivity and specificity, but the need for expensive machinery and well-trained personnel slow down the disease detection. The emerging Cas12a-based method presents a new technique for nucleic acid detection. However, it is time-consuming and labor-intensive when used for HPV detection, as several reactions are required in order to identify multiple HPV infections. We herein present a non-genotyping method for 13 types of HR-HPV detection in a single reaction by combining the isothermal recombinase polymerase amplification (RPA) method with CRISPR-Cas12a technology. The result could be achieved in 35 min with high sensitivity (500 copies per reaction). This assay represents great advances for the application of RPA-Cas12a system and holds a great potential to address the key challenges facing the HPV diagnostics.

This paper proposes a mixture regression model-based method for drug sensitivity prediction. The proposed method explicitly addresses two fundamental issues in drug sensitivity prediction, namely, population heterogeneity and feature selection pertaining to each of the subpopulations. The mixture regression model is estimated using the imputation-conditional consistency algorithm, and the resulting estimator is consistent. This paper also proposes an average-BIC criterion for determining the number of components for the mixture regression model. The proposed method is applied to the CCLE dataset, and the numerical results indicate that the proposed method can make a drastic improvement over the existing ones, such as random forest, support vector regression, and regularized linear regression, in both drug sensitivity prediction and feature selection. The p-values for the comparisons in drug sensitivity prediction can reach the order O(10-8) or lower for the drugs with heterogeneous populations.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1–10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.

Nanoparticle-induced treatments can promote seed germination and improve germination potential under environmental stresses such as drought and salinity. This study aimed to investigate the effects of Zinc oxide nanoparticles (ZnONPs) on soybean seed germination and to develop a precise evaluation method. We developed a full-time sequence crop growth vitality monitoring system. Using germination rate and root length as primary evaluation indicators, we conducted full-time sequence germination vitality monitoring experiments on soybean seeds treated with ZnONPs. A dataset was constructed from images documenting embryonic root growth. The developed detection model was used to evaluate image detection accuracy during germination. Germination index and embryonic root length were also calculated. Further tests were performed on seeds exposed to 600 mg/L ZnONPs dispersion, followed by treatment with different concentrations of NaCl and PEG6000 solutions. At a concentration of 600 mg/L ZnONPs dispersion, soybean seeds showed the highest germination rate (an increase of 28%) and the longest radicle length (an increase of 42%). Compared with deionized water, the 600 mg/L ZnONPs dispersion accelerated initial germination time, increased germination rate, and enhanced radicle length under low-concentration stress. The results indicate that, at certain concentrations, ZnONPs dispersion positively influences soybean seed germination under varying salinity and drought conditions. We examined morphological and physiological changes in ZnONPs-treated seeds under stress, establishing a preliminary foundation for evaluating crop and variety vitality. These findings provide new insights that may contribute to improving soybean germination under simulated stress conditions, serving as a preliminary theoretical reference for potential applications in arid and saline environments.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.

Background N4-acetyldeoxycytosine (4acC) is a recently identified DNA modification that has been detected across multiple species. However, previous studies have largely focused on Arabidopsis , and the distribution and function of 4acC in other plant species poorly understood. Results In this study, we generated a genome-wide map of 4acC in rice and conducted a feature-level comparison with Arabidopsis . Although 4acC in rice shows a more uniform chromosomal distribution and is more frequently located in intergenic regions, it exhibits conserved associations with transcriptional activation in both species. Specifically, 4acC is significantly enriched in open chromatin regions, transcription factor binding sites, and activating histone modifications, and its modification levels are generally independent of 5-methylcytosine (5mC). Functionally, 4acC is associated with alternative splicing, particularly intron retention events. Evolutionary and population genetic analyses show that 12.8% of one-to-one orthologous genes carry 4acC in both species, a proportion significantly higher than expected by chance, and that 4acC is preferentially localized to genomic regions with trait-associated QTLs. Conclusions In conclusion, our results reveal that 4acC is a conserved DNA modification with potential roles in plant phenotypic variation, adaptive evolution, and post-transcriptional regulation, providing new insights into its epigenetic function.

Wounds occur when skin integrity is broken and the skin is damaged. With progressive changes in the disease spectrum, the acute wounds caused by mechanical trauma have been become less common, while chronic wounds triggered with aging, diabetes and infection have become more frequent. Chronic wounds now affect more than 6 million people in the United States, amounting to 10 billion dollars in annual expenditure. However, the treatment of chronic wounds is associated with numerous challenges. Traditional remedies for chronic wounds include skin grafting, flap transplantation, negative-pressure wound therapy, and gauze dressing, all of which can cause tissue damage or activity limitations. Nanobiotechnology--which comprises a diverse array of technologies derived from engineering, chemistry, and biology--is now being applied in biomedical practice. Here, we review the design, application, and clinical trials for nanotechnology-based therapies for chronic wound healing, highlighting the clinical potential of nanobiotechnology in such treatments. By summarizing previous nanobiotechnology studies, we lay the foundation for future wound care via a nanotech-based multifunctional smart system. Keywords: nanobiotechnology, chronic wound healing, scaffold systems, cell-carrying systems, stimuli-responsive systems

The preferred treatment for acute ischaemic stroke (AIS) is intravenous thrombolysis (IVT) administered within 4.5 hours (h) of symptom onset. This study aimed to identify metabolomic biomarkers for distinguishing AIS patients within 4.5 h of symptom onset, addressing the often exclusion of those with unknown onset times from IVT. In this retrospective case-control study with 30 AIS patients, early AIS with onset time within 0–4.5 h (ES, n  = 16) and late AIS within 4.5–24 h (LS, n  = 14) groups were differentiated. Their complete sets of plasma metabolites were examined. A stepwise analysis was performed to identify potential biomarkers. Biliverdin and Nicotinamide N-oxide (NAMO) emerged as potential biomarkers, combined to achieve a high AUC of 0.964 (95% Confidential interval 0.900–1), a specificity of 100% (78.47–100%), and a sensitivity of 93.75% (71.67–98.89%) for AIS onset time determination. These metabolites show promise as molecular clocks for determining the onset time of AIS, potentially extending IVT access to patients with unknown onset times. However, their clinical applicability necessitates rigorous validation in larger and independent cohorts to establish their role in improving AIS management through extended IVT accessibility.

Background Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson’s disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD. Methods We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments. Results During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)). Conclusion Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.