Phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein PINLYP regulates type I interferon innate immunity.

Type I interferons (IFNs) are the first frontline of the host innate immune response against invading pathogens. Herein, we characterized an unknown protein encoded by phospholipase A2 inhibitor and LY6/PLAUR domain-containing (PINLYP) gene that interacted with TBK1 and induced type I IFN in a TBK1- and IRF3-dependent manner. Loss of PINLYP impaired the activation of IRF3 and production of IFN-ß induced by DNA virus, RNA virus, and various Toll-like receptor ligands in multiple cell types. Because PINLYP deficiency in mice engendered an early embryonic lethality in mice, we generated a conditional mouse in which PINLYP was depleted in dendritic cells. Mice lacking PINLYP in dendritic cells were defective in type I IFN induction and more susceptible to lethal virus infection. Thus, PINLYP is a positive regulator of type I IFN innate immunity and important for effective host defense against viral infection.

Performance of indocyanine green in sentinel lymph node mapping and lymph node metastasis in penile cancer: systematic review, meta-analysis, and single-center experience.

PURPOSE: The aim of this study was to investigate the overall sensitivity and specificity of indocyanine green (ICG)-near-infrared (NIR) fluorescence imaging in the detection of sentinel lymph node metastasis (SLNM) in penile cancer. METHODS: We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases to identify manuscripts where ICG was intravenously administered prior to or during penile cancer surgery, with no restriction on language or publication status. The results extracted are presented as forest plots. RESULTS: Seven studies were included in the analysis. The median sensitivity and specificity of ICG-NIR imaging for SLNM detection were 100 and 4%, respectively; the pooled sensitivity was 100.0% (95% confidence interval [CI] 97.0-100.0) and specificity was 2.0% (95% CI 1.0-3.0). There was no significant difference in the diagnostic results between different injection sites and doses in each experimental group. CONCLUSION: To our knowledge, this meta-analysis is the first to summarize the diagnostic performance of ICG-NIR imaging for SLNM detection in penile cancer. ICG is sensitive in the imaging of SLN tissue, which can consequently improve the accuracy of lymph node detection. However, the specificity is very low.

[Herbalogical analysis of Aconiti Carmichaeli Radix].

Tianxiong has been used as a Chinese medicinal in China for thousands of years, and the earliest record can be traced back to the Shennong's Classic of Materia Medica. It is effective in dispersing wind, dissipating cold, and replenishing fire to streng-then yang. To clarify the origin of Tianxiong, the present herbalogical study reviewed the ancient and modern literature from the origin, processing, and clinical efficacy. Before the Tang Dynasty, although the description of Tianxiong was quite superficial, an apparent difference between Tianxiong and Fuzi was recognized. In the Tang and Song Dynasties, Tianxiong and Fuzi were mistakenly recognized to be prepared from a same plant since their raw materials came from artificial cultivation. Medical literature in the Ming and Qing Dynasties mostly followed the previous records, with the origin of Tianxiong remaining controversial. There were three mainstream views about the origin of Tianxiong according the ancient medical books. First, Tianxiong was a kind of Aconiti Radix(Chuanwu) without attachment of Fuzi. Second, Tianxiong was the large Fuzi. Third, Tianxiong derived from Aconiti Kusnezoffii Radix(Caowu) about 10 cm in length. By contrast, Fuzi in a large size was simply regarded as Tianxiong in modern times. The processing methods were diversified in the ancient times, and the fire-processing was continuously applied. With the deepening of the research on the efficacy and detoxification mechanism, more methods were discovered, such as processing with ginger juice, child's urine and alcohol. As for modern times, the processing of Tianxiong has not been nearly passed down. The characteristic processing of Tianxiong only handed down in Sichuan province and Lingnan area, which can be discriminated by the last step. The efficacies of Tianxiong can be directly understood from its literal name, including dispersing wind, dissipating cold, and replenishing fire to assist yang. Nowadays, Tianxiong is mostly used to strengthen yang.

Regulation of gammaherpesvirus lytic replication by endoplasmic reticulum stress-induced transcription factors ATF4 and CHOP.

The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling cross-talks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK. Both Bip and the downstream transcription factor ATF4 inhibited BCR-mediated MHV68 lytic gene expression, whereas UPR-induced C/EBP homologous protein (CHOP) was required for and promoted BCR-mediated MHV68 lytic replication by suppressing upstream Bip and ATF4 expression. Bip knockout was sufficient to rescue BCR-mediated MHV68 lytic gene expression in CHOP knockout cells, and this rescue was blocked by ectopic ATF4 expression. Furthermore, ATF4 directly inhibited promoter activity of the MHV68 lytic switch transactivator RTA. Altogether, we show that ER stress-induced CHOP inhibits Bip and ATF4 expression and that ATF4, in turn, plays a critical role in CHOP-mediated regulation of BCR-controlled MHV68 lytic replication. We conclude that ER stress-mediated UPR and BCR signaling pathways are interconnected and form a complex network to regulate the gammaherpesvirus infection cycle.

Murine Gammaherpesvirus 68: A Small Animal Model for Gammaherpesvirus-Associated Diseases.

Murine gammaherpesvirus 68 (MHV68) is a naturally occurring pathogen of murid rodents that is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). Viral, immunologic, and disease parameters following experimental infection of laboratory mice with MHV68 closely resemble what occurs during primary EBV infection of humans, which suggests that MHV68 infection of mice offers a small animal model to study in general the pathogenesis of gammaherpesvirus infections. Diseases elicited by MHV68 infection include lymphoproliferative diseases, idiopathic pulmonary fibrosis, and autoimmune diseases, ailments also associated with EBV infection of humans. Furthermore, MHV68 infection also is linked to the development of vasculitis, encephalomyelitis, and other disorders that resemble pathologies with viral and nonviral etiologies in humans. This review aims to provide an overview of MHV68-associated diseases in infected mice that may provide a model for understanding basic mechanisms by which similar diseases in humans occur and can be treated.

Gaussian processes modeling for the prediction of polymeric nanoparticle formulation design to enhance encapsulation efficiency and therapeutic efficacy.

Conventional drugs have been facing various drug delivery obstacles, including first-pass metabolism for oral medications, drug degradation by cellular enzymes, off-target effects, and cytotoxicity of healthy cells. Nanoparticles (NP) application in drug delivery can compensate for these drawbacks to a great extent. NPs can be fabricated using different materials and structures to achieve desired therapeutic effects. For each type of NP material, its physicochemical properties determine compatibility with specific drugs and other supplemental compositions. The optimized material selection becomes prominent in NP development to improve NP performances. Due to the nature of NP fabrication, the process is long and expensive. To accelerate NP composition optimization, machine learning (ML) techniques are among the most promising methods for efficient data predictions and optimizations.As a proof-of concept, we created Gaussian Process (GP) models to make predictions for drug encapsulation efficiency (EE%) and therapeutic efficacy of 32 poly (lactic-co-glycolic acid) (PLGA) NPs that are formed with materials with different physicochemical properties. Two model drugs, doxorubicin (DOX) and docetaxel (DTX) were loaded separately. The IC50 values for the various NPs formulations were evaluated using the OVCAR3 epithelial ovarian cancer cell line. EE% GP model has the highest prediction accuracy with the lowest normalized root-mean-squared-error (RMSE) of 0.187. The DOX and DTX IC50 GP models have normalized RMSEs of 0.296 and 0.206, respectively, which are higher than that of the EE% GP model.

Self-certification: A novel method for increasing sharing discernment on social media.

The proliferation of misinformation on social media platforms has given rise to growing demands for effective intervention strategies that increase sharing discernment (i.e. increase the difference in the probability of sharing true posts relative to the probability of sharing false posts). One suggested method is to encourage users to deliberate on the veracity of the information prior to sharing. However, this strategy is undermined by individuals' propensity to share posts they acknowledge as false. In our study, across three experiments, in a simulated social media environment, participants were shown social media posts and asked whether they wished to share them and, sometimes, whether they believed the posts to be truthful. We observe that requiring users to verify their belief in a news post's truthfulness before sharing it markedly curtails the dissemination of false information. Thus, requiring self-certification increased sharing discernment. Importantly, requiring self-certification didn't hinder users from sharing content they genuinely believed to be true because participants were allowed to share any posts that they indicated were true. We propose self-certification as a method that substantially curbs the spread of misleading content on social media without infringing upon the principle of free speech.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Advanced flow cytometry for biomedical applications.

Flow cytometry (FC) is a versatile tool with excellent capabilities to detect and measure multiple characteristics of a population of cells or particles. Notable advancements in in vivo photoacoustic FC, coherent Raman FC, microfluidic FC, and so on, have been achieved in the last two decades, which endows FC with new functions and expands its applications in basic research and clinical practice. Advanced FC broadens the tools available to researchers to conduct research involving cancer detection, microbiology (COVID-19, HIV, bacteria, etc.), and nucleic acid analysis. This review presents an overall picture of advanced flow cytometers and provides not only a clear understanding of their mechanisms but also new insights into their practical applications. We identify the latest trends in this area and aim to raise awareness of advanced techniques of FC. We hope this review expands the applications of FC and accelerates its clinical translation.

Efficacy and safety of abdominal acupuncture in Parkinson's disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Parkinson disease (PD) is a worldwide spread neurodegenerative disorder. Dopamine replacement therapy is currently the mainstream treatment, which can alleviate the symptoms but induces motor complications. Acupuncture therapy is effective for PD. As a form of acupuncture, the abdominal acupuncture has been used to relieve symptoms in patients with PD, but its effectiveness and safety have not yet reached a definitive conclusion. Therefore, this systematic review and meta-analysis protocol is planned to evaluate the efficacy and safety of abdominal acupuncture for PD patients. METHODS: Six English databases (PubMed, Web of Science, MEDLINE, EMBASE, Springer Cochrane Library, and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan Fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to August 20, 2022. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The analysis will be conducted by RevMan 5.3 software according to Cochrane Handbook. RESULTS: The aim of this systematic review is to provide high-quality evidence to assess the efficacy and safety of abdominal acupuncture for patients in Parkinson's disease. The efficacy and safety of abdominal acupuncture for PD will be comprehensively assessed from the outcomes, including the effectiveness rate. The Unified Parkinson Disease Rating Scale (UPDRS) and Webster scale, Motor symptom scores utilizing UPDRS III scale, Dopamine (DA) content, and Nonmotor symptom scores employing UPDRS I scale, Activities of daily living using UDPRS II; Complications of treatment applying UPDRS IV, antioxidant ability: super oxide dismutase activity and Lipide Peroxide (LPO) content, Content of inflammatory cytokines, tumor necrosis factor-α and interleukin-1ß, and adverse events as the secondary outcome. CONCLUSION: This systematic review will explore whether abdominal acupuncture is an effective and safe intervention for patients in Parkinson's disease.

Dimethyl sulfoxide (DMSO) is a stabilizing co-solvent for G-quadruplex DNA.

We report the effect of dimethyl sulfoxide (DMSO) on the stability of the four-stranded structures formed by the oligodeoxyribonucleotides d[5'-AGGG(TTAGGG)3-3'] (HTel), d[5'-(GGGT)3GGG-3'] (G3T), d[5'-GGTTGGTGTGGTTGG-3] (TBA), d[5'-GGGGTTTTGGGG-3'] (Oxy-1.5), and d[5'-TGGGGT-3'] (TG4T). In these measurements, influence of the co-solvent was assessed by the change in the mid-point of the heat-induced unfolding, Tm, by monitoring the change in the UV absorption of the sample. Increasing concentrations of DMSO led to an increase in the Tm from the folded to unfolded states. We have also studied the effect of the denaturant urea and mixtures of urea and DMSO on the stability of the intramolecular HTel and the intermolecular TG4T G-quadruplexes. Consistent with earlier data, we found that urea destabilized the folded G-quadruplex structure; the Tm decreases with increasing urea concentration. However, in solutions containing both urea and DMSO, we observed that the two co-solvents off-set the destabilizing and stabilizing effect, respectively, of one another. That is, in solutions containing urea, increasing concentrations of DMSO led to the increase of the Tm of the G-quadruplex structure. This effect is observed in solutions containing sodium, potassium, or ammonium as the ion that stabilizes the folded G-quadruplex structure. The complementary effect of the two co-solvents presumably arises from differential interactions between urea and DMSO and the oligonucleotide or the cations involved in the stabilization of the G-quadruplexes. These results highlight the importance of co-solutes and co-solvents in systems containing guanine-rich DNA, particularly experimental processes that require DMSO.

6-Aminopyridine-3-boronic acid functionalized magnetic nanoparticles for highly efficient enrichment of cis-diol-containing biomolecules.

Boronate affinity materials, as efficient sorbents for extraction, separation and enrichment of cis-diol-containing biomolecules, have attracted more and more attention in recent years. However, conventional boronate affinity materials require a basic binding pH (usually 8.5), which gives rise to not only inconvenience in operation but also the risk of degradation of labile compounds, and suffer from low binding affinity, which make the extraction of cis-diol-containing compounds of low concentration difficult or impossible. In order to reduce the binding pH to neutral or acidic conditions and improve binding affinity, we present a type of material, 6-aminopyridine-3-boronic acid functionalized magnetic nanoparticles, with affinity towards cis-diol-containing biomolecules. 6-Aminopyridine-3-boronic acid, exhibiting low binding pH, high affinity and excellent water solubility toward cis-diol-containing compounds, was first employed as an affinity ligand. The result indicated that the boronate affinity MNPs exhibited low binding pH (5.0) and high binding affinity toward cis-diol-containing biomolecules. Such a property enabled the selective extraction of cis-diol-containing biomolecules with low concentration under neutral or acidic conditions. This feature greatly favored the selective enrichment of cis-diol-containing biomolecules with low concentration from real samples. The feasibility for practical applications was demonstrated with the selective enrichment of cis-diol-containing biomolecules with low concentration in a human urine sample.

The scientific elucidation of daodi medicinal materials.

Daodi medicinal materials (DMMs), with unique characteristics and specific ecological growing environments, are recognized as high-quality medicinal products of Chinese medicinal materials (CMMs). The quality evaluation of CMMs is fundamental for standardization. The concept and application of DMMs have a long history as described in records in ancient books and rooted in practice and experience over generations. DMM is the specific term for pure, superior medicinal herbs with the following characteristics: optimum harvest season (reflecting the appropriate developmental stage of the plant), scrupulous processing, traditional preparation technology, etc. As DMM and high-quality medicinal products are traditionally thought to be closely related, modern scientific studies that confirm the association of these products are described. This article aims to clarify the scientific elucidation of DMMs.